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"Prior work has shown that Class I PI3Ks inhibit autophagy by activating AKT, which promotes MTOR signaling, thus suppressing autophagy [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

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"PI3K triggers Akt which consequently activates mTOR."

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"The activation of the PI3K and AKT signaling pathway stimulates mTOR signaling cascades, modulating two master molecules associated with the initiation of mRNA translation, namely, 70-kDa ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E binding protein 1 (4EBP1)."

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"More specifically, in nutrient rich conditions or stimulation by growth factors, Akt activates mTOR Complex 1 (mTORC1), suppressing autophagy by phosphorylation-dependent inhibition of Unc-51 like-autophagy activating kinase 1/2 (ULK1/2) and the Vacuolar protein sorting 34 (Vps34) complex [ xref ]."

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"Moreover, Akt activation can also activate the mTOR pathway, but its effect is weaker than Ras-Erk pathway XREF_BIBR, XREF_BIBR."

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"Since mTOR is activated by Akt, although it is not clear if this is a direct or indirect activation [reviewed in [XREF_BIBR]], we decided to monitor if Akt was activated by IR by studying its phosphorylation state, which was reported to be an early response to IR [XREF_BIBR, XREF_BIBR]."

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"MAPK/ERK mediates the mitogenic effects of IGF-1 signaling whereas PI3K/AKT promotes mTOR-controlled cell growth and metabolism (Goto et al., 2009)."

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"In these studies, inhibition of AKT mediated mammalian target of rapamycin (mTOR) activity using the macrolide rapamycin resulted in reduced optic glioma volume and proliferation."

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"The mechanistic target of rapamycin (mTOR) is also activated by AKT and increases the level of HIF-1α, which can directly increase the expression of vascular endothelial growth factor (VEGF) or bind to HIF-1β in hypoxia conditions and transfer to the nucleus to promote the expressions of erythropoietin (EPO) and VEGF."

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"Evidence of mTOR Activation by an AKT Independent Mechanism Provides Support for the Combined Treatment of PTEN Deficient Prostate Tumors with mTOR and AKT Inhibitors."

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"The PI3K and Akt mediated activation of mTOR is antagonized by the 5 '-adenosine monophosphate kinase (AMPK), the major sensor of cellular energy charge."

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"Activation of mTOR by Akt stimulates protein synthesis through the actions of the ribosomal protein S6 kinase (S6K) and the translational initiation factor eIF-4E-binding protein 1 (4EBP1)."

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"AKT can activate mTOR indirectly promoting the dissociation of the tuberous sclerosis complex 2 (TSC2), which sequesters mTOR."

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"AKT indirectly activates mTOR, whose kinase activity is critical for preparing activated T cells for the bioenergetic demands of clonal expansion."

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"Consistently, tumour-suppressor genes involved in the upstream inhibition of mTOR signaling (PTEN, TSC1, and TSC2) turn autophagy on, and conversely, mTOR activating oncogene products such as class I PI3K and Akt genes turn it off [XREF_BIBR - XREF_BIBR]."

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"MTOR regulated multiple cell growth and cellular functions by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. xref mTOR is activated by Akt."

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"Furthermore, radiation exposure has been intimately linked to increased reactive oxygen species (ROS) production and persistent oxidative stress in cells, and oxidative stress has been reported to activate the pro growth PI3K and Akt pathway, which in turn is known to activate mTOR [XREF_BIBR, XREF_BIBR]."

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"Although it is not clear precisely how Akt may activate mTOR, recent evidence suggests the tuberous sclerosis complex, an autosomally dominant tumor suppressor complex involved in the tuberous scleros[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"The regulation of cell size by Pdk1 involves the Akt mediated activation of mTOR."

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"MTOR is activated by Akt and ultimately blocks apoptosis and increases proliferative potential of cancer cells."

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"XREF_BIBR, XREF_BIBR Nevertheless, considerable evidence exists to show that insulin can enhance the activation of mTOR via stimulation of 4EBP1 binding to dimeric mTOR complex 1, XREF_BIBR and mediated by the Akt and PKB substrate PRAS40 (proline rich Akt and PKB substrate 40 kDa)."

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"In a GBM orthotopic xenograft model, it was shown however that PTEN does not serve as a predictive marker for RAD001 effectiveness, despite the importance of PI3K and AKT signaling activation in mTOR upregulation [XREF_BIBR]."

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"As shown in XREF_FIG, reactivation of Akt and mTOR signaling by forced expression of Akt antagonized the upregulated LC3-II and cleaved PARP level induced by crocin in HepG2 and HCCLM3 cells."

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"However, Akt activation also activates the mammalian target of rapamycin complex 1 (mTORC1) which induces skeletal muscle hypertrophy."

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"Akt activates mTOR through at least two mechanisms: either directly by phosphorylating mTORC1 at S2448 ( xref ) or indirectly through TSC2."

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"T cell receptor together with CD28 co-stimulation activates 3-phosphoinositide-dependent protein kinase 1 (PI3K-1) and Akt, which in turn activate the central metabolic regulator mammalian target of rapamycin (mTOR)."

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"The AKT pathway crosstalks with and activates the mTOR pathway [XREF_BIBR], which raises the possibility that LIF activates the mTOR pathway through AKT."

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"AKT has been shown to activate mTOR directly through the phosphorylation or indirectly through tuberous-sclerosis-complex-dependent mechanism [XREF_BIBR]."

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"Activation of mTORC1 requires AKT dependent activation of mTOR via heterotrimeric tuberous sclerosis complex (TSC) and the monomeric GTPase, Ras homolog enriched in brain (Rheb) ( xref )."

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"Akt activates mTOR and thus inhibits autophagy in β-cells [ xref ]."
| PMC

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"AKT also activates the serine/threonine kinase activity of mTOR kinase, which is the active component of two multi protein complexes, TORC1 and TORC2 [XREF_BIBR, XREF_BIBR]."

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"TGF-beta-mediated AKT signaling, downstream of PI3K may further activate mTOR signaling."

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"These results demonstrated that mTOR activation is mediated by the PI3K and Akt pathway through Notch induced inhibition of PTEN in K562R IMT cells."

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"Under normal conditions, phosphorylated PI3K phosphorylates Akt, which inhibits tuberous sclerosis complex 1/2 (TSC1/2) and then activates mTOR."

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"Although Akt activity enhances mTOR activity, the dynamic interplay between these two molecules is complex (XREF_FIG)."

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"MTOR, another serine threonine protein kinase, is activated by Akt and plays an important role in cell growth by monitoring cellular needs, such as nutrients, oxygen, and energy."

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"108 Elevated AKT phosphorylation and/or activated mTOR functioning arises in 70% of malignant melanomas."

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"Akt phosphorylates and thereby activates mTOR to inhibit autophagy, whereas AMP-activated protein kinase (AMPK), which is a key energy sensor and that regulates cellular metabolism to maintain energy homeostasis, promotes autophagy ."

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"As an essential Akt independent mediator of the PI3K and mTOR signaling pathway, SGK1 is transcriptionally and posttranslationally affected by various factors, including hormones, cytokines, and stress response."

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"To promote protein synthesis and hypertrophy, Akt indirectly activates mTOR while simultaneously inhibiting glycogen synthase kinase 3b (GSK3b)."

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"PIK3CA mutations are associated with activation of mTOR, but not AKT signaling pathway."

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"For example, mutations in phosphatase and tensin homolog deleted on chromosome ten, which occur in approximately 10% of melanomas (Gray-Schopfer et al., 2005), would be predicted to activate Akt, whic[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Therefore, by acting on TSC2, AKT induces the activity of mTOR and the downstream events of mTOR activation that include metabolic changes, protein translation as well as cell proliferation."

eidos
"Activation of AKT stimulates mTOR signaling ."

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"Taken together, these data suggest that in response to the presence of intracellular Salmonella, FAK may be required for Akt mediated activation of mTOR, and that this leads to the activation of p70S6K but not 4EBP."

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"The interaction between Ca 2+ signalling, PKA and mTOR signalling has been postulated by several groups, where PKA phosphorylates Akt and PKB, which in turn activates mTOR [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."

eidos
"MTOR belongs to the PI3K-related kinases family and is activated by Akt ( Costa-Mattioli & Monteggia , 2013 ) ."

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"Akt activates mTOR via phosphorylation and inactivation of tuberous sclerosis complex-2 (TSC-2)."

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"Akt can activate mTOR by phosphorylating and inactivating the tumor suppressor protein tubersclerosis complex 2 (TSC2), which negatively regulates mTOR activity."

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"A recent study also revealed the role of LKB1 as an indispensable gatekeeper for the primordial follicle pool through elevated mTOR signalling by an AKT independent LKB1-AMPK pathway 15."

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"Several downstream targets including the serine/threonine kinase Akt that activates mTOR are activated by PI3K. Furthermore, activation of this pathway is known to decrease sensitivity to chemotherapeutics as well as to irradiation (IR)[ xref , xref ], resulting in a limited treatment outcome."

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"These results suggest that while Akt signaling is upregulated in IGFIR structures, the hyperproliferation phenotype and anti-apoptotic signaling were not mediated solely through Akt activation of raptor and mTOR signaling."

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"The mTOR is associated with increased cell proliferation and is activated by Akt."

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"Taken together, these data suggest that activation of Akt in dystrophin deficient mice appears to stimulate the mTOR dependent pathway in concert with disease progression while the mTOR-independent an[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"The AKT kinase pathway activates mTOR which results in cells proliferation."

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"The time course of activation of Akt showed that its phosphorylation occurred later than the peak activation of mTOR and p70S6k, suggesting a major Akt independent activation of mTOR."

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"rapamycin, an inhibitor of mTOR, did not affect the viability of the transgenic lymphocytes or lymphoma cells, confirming that mTOR is not targeted by Akt activation in LMP1 transgenic lymphocytes or malignant lymphoma cells (XREF_FIG)."

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"[XREF_BIBR] Moreover, the PI3k-Akt pathway is an important regulator of cell proliferation and is thought to mediate the effects of mTOR."

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"Phosphorylated Akt activates mTOR, a major regulator of protein translation."

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"In this cascade, the lipid kinase, PI3K activates its major downstream effector Akt which in turn activates mTOR [ xref ]."

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"It is worth noting that mTOR activation by the PI3K and AKT pathway depends on the action of PS, XREF_BIBR which brings AKT to the plasma membrane where it can be activated by PIs."

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"XREF_BIBR In addition, this same group showed that pharmacological activation of TGR5 in bone marrow derived macrophages, reduced lipopolysaccharide induced chemokine production by a mechanism that required AKT dependent activation of mTOR complex 1 (mTORC1), which stimulated production of the dominant negative CCAAT and enhancer binding protein isoform, liver inhibitory protein."

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"Moreover, AKT can indirectly activate mTOR, which is a protein kinase critical for cell proliferation deregulated in GBM [ xref , xref ]."

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"MTOR is modulated by PI3K/Akt pathway, and the activation of the PI3K/Akt/mTOR pathway could inhibit excessive autophagy and block the cardiac disease progress (32)."

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"Activated AKT (or p-AKT) could further activate mTOR by phosphorylation, which could regulate cell stress response and cell cycle."

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"Moreover, MANF enhanced neurite outgrowth and Akt and mTOR and Erk and mTOR activation can also be blocked by inhibition of Akt, Erk or mTOR."

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"The present study demonstrates an association between IGF-1R and the phosphatidylinositol 3-kinase (PI3K)/threonine protein kinase B (Akt)/mammalian target of rapamycin mTOR signaling pathway and autophagy."

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"Phosphorylation of AKT can activate the serine/threonine kinase mTOR that acts as an important upstream regulator of autophagy XREF_BIBR."

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"MTOR itself is be activated by PI3K and Akt signaling initiated by TCR activation and costimulation, and it has been reported that HIF-1 induction upon TCR activation is dependent on both PI3K and Akt as well as mTOR."

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"Although Akt has been shown to activate mTOR 30, we did not observe substantial involvement of mTOR in the Akt-HSF-1-Slug mediated promotion of EMT in HER2 amplified breast cancer cells we have examined."

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"Activated AKT further activates mTOR by inhibiting the tuberous sclerosis complex (TSC1/2), which is an inhibitor of mTOR."

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"For FLSs, we clearly observed an AKT-dependent activation of mTOR upon TNF stimulation."

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"To be specific, PI-3K and Akt increases the synthesis of HIF-1alpha by activating FRAP (FK506 binding protein-Rapamycin Associated Protein), a kinase that enhances the translation rate of hif-1alpha mRNA [XREF_BIBR]."

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"AKT then activates mTOR, a serine/threonine kinase involved in cell proliferation, cell growth and angiogenesis."
| PMC

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"A decrease in Akt phosphorylation would decrease mTOR activation, abrogating Otub1 protein expression and thus resulting in the re-expression of GRAIL and inhibition of cell proliferation."

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"It was reported that AKT on the one hand activates mTOR, which increases EF2 activity XREF_BIBR."

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"AMPK has also been reported to counteract AKT mediated activation of mTOR in response to UV radiation and together with activation of p53 accounts for the pro apoptotic pathways downstream from ROS activated growth factors receptors [XREF_BIBR, XREF_BIBR]."

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"This may be due in part to the presence of numerous negative feedback mechanisms on mTOR signaling that can lead to activation of upstream proteins, including AKT."

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"These proteins include the PDK1 and AKT kinases, which cause activation of mTOR-dependent signaling, protein translation, and ribosomal biogenesis (Alessi et al., 1997; Dibble and Cantley, 2015; Ma and Blenis, 2009; Manning and Toker, 2017)."

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"To determine how Akt may regulate Glut1, we analyzed the role of Akt activation of mammalian target of rapamycin (mTOR)/regulatory associated protein of mTOR (RAPTOR) and inhibition of glycogen synthase kinase (GSK)3."

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"In contrast, loss of Akt activity prevents mTOR signaling."

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"119 In this study, PCAF expression inhibited the phosphorylation of Akt and mTOR kinase, whereas knockdown of PCAF stimulated Akt and mTOR kinase activity."

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"Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity."

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"AKT then phosphorylate and activate downstream signaling molecular mammalian target of rapamycin (mTOR)."

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"The mTOR activity is negatively regulated by the tuberous sclerosis complex (TSC) composed of TSC1 and TSC2; AKT activates mTOR by inhibiting TSC."

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"We propose that the activation of mTOR by Akt-mediated cellular energy and inhibition of AMPK is the predominant pathway by which Akt activates mTOR in vivo."

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"On the other hand, AKT activates mTOR by inhibitory phosphorylation of TSC2 protein."

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"The mTOR kinase serves as a gatekeeper for autophagy induction : the activation of mTOR by Akt and MAPK signaling suppresses autophagy, and the inactivation of mTOR by AMPK and p53 signaling promotes autophagy."

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"Previous studies have also indicated that the activation of PI3K-Akt pathway up-regulates mTOR and decreases autophagy in different cell types [XREF_BIBR, XREF_BIBR]."

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"AKT is known to cause downstream mTOR activation [XREF_BIBR], and since mTOR increases translation of many proteins, we tested if mTOR was responsible for the increased p21 levels in the urothelial cell lines stimulated with growth factors."

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"Akt activated mTOR, which in turn phosphorylates p70-S6 kinase, leads to the activation of the ribosomal S6 protein."

eidos
"Inhibition of AKT decreased mTOR activation and increased autophagy , demonstrating that AKT may act upstream of mTOR to quench autophagy during cisplatin treatment ."

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"We further assumed that AKT constantly decays at rate d , yielding(3)y2′(t)=a2+k1y1+kSy8n2ξ28n2+y8n2-d2y2.Following the literature (32) we assumed that AKT activates mTOR (y ) at rate k ."

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"Translation of MYC mRNA is partly regulated by mammalian target of rapamycin (mTOR), which is activated by AKT after its phosphorylation by phosphoinositide 3-kinase (PI3K) [XREF_BIBR]."

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"The PI3K-AKT-mTOR axis could be considered to be a single pathway [ xref ] in which AKT activates mTOR to control cell proliferation and growth in response to environmental stimuli by phosphorylating and inactivating the mTOR suppressors tuberous sclerosis protein 1 (TSC1) and TSC2 [ xref , xref ]."

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"In canonical growth factor signaling, mTOR is activated by PI3K/Akt, through IGF-1 and insulin signaling, but a considerable body of evidence suggests that mTORC1 is also likely activated by a growth factor-independent movement of proteins to and from the lysosome, via resistance exercise-induced phosphorylation of TSC2 [77]."

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"PI3K and AKT mediated activation of the downstream target mTOR results in cell proliferation and survival by regulating the translation of proteins involved in tumor progression [XREF_BIBR, XREF_BIBR]."

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"PI(3,4,5)P3 synthesis catalyzed by PI3K phosphorylation contributes to the activation of a wide range of downstream targets, including Akt, which activates mammalian target of rapamycin (10) ."

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"MTOR forms two functionally distinct complexes, mTORC1 and mTORC2, the activities of both being dependent on the activation of mTOR by AKT within the complex [ xref ]."

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"Akt, a serine/threonine specific protein kinase, stimulates mTOR, resulting in protein synthesis increasing via its effectors 4EBP1 and S6K [XREF_BIBR - XREF_BIBR], promoting polysome formation and translation of transcription factors modulating tumour cell growth."

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"Akt mediated AKG in active mTOR signaling pathway."

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"Akt also serves to activate Mammalian Target of Rapamycine (mTOR), which mediates the fibroblast response to TGF-β [97] and MMP1-inhibition, preventing its proteolytic collagenase activity [98]."

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"The phosphorylation of AKT directly stimulates mTOR, which is a ubiquitous serine threonine protein kinase."

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"It was reported that Akt activates mTOR by phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2)."

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"PIP3 recruits and activates AKT and mTOR is activated by the activities of PI3K and AKT."

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"Upon phosphorylation, Akt is able to activate mammalian target of rapamycin (mTOR), which, in turn, activates 70-kD ribosomal S6 protein kinase xref and inhibits eukaryotic translation initiation factor 4E binding protein-1/PHAS-1; xref these processes stimulate MPS."

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"Activation of mTORC1 requires AKT dependent activation of mTOR via heterotrimeric tuberous sclerosis complex (TSC) and the monomeric GTPase, Ras homolog enriched in brain (Rheb)."

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"It is reported that mTOR could be activated by MAPK/ERK1/2 and pI3k and Akt pathways, 11 therefore ERK1/2 and Akt were detected with western blot."

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"With the addition of weak stimulation, Akt signaled to GSK3 and mTOR, a gating effect that was mediated by voltage dependent Ca (2+) channels and the Wnt pathway."

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"For example, activation of mTOR signaling by AKT leads to activation of NF-kappaB, and this appears to involve an association of IKK with Raptor within the mTORC1 complex [XREF_BIBR]."

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"Numerous studies have documented the ability of IGF-1 to induce muscle hypertrophy by Akt activation of mTOR signaling."

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"One of the most important sensors involved in the regulation of mTOR activity is PI3K, which enhances the phosphorylation of Akt and subsequently activates mTOR."

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"As shown in XREF_FIG, Akt overexpression almost reactivated the activity of Akt and mTOR and suppressed autophagy in HepG2 and HCCLM3 cells treated with crocin."

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"Moreover, acurrent study showed that the activation of PI3K and AKT stimulates mTOR, which regulates cells by helping them suppress autophagy followed by cell death involving the regulation of LC3-I, [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"As discussed above, past studies have demonstrated that Akt phosphorylation may activate the mTOR pathway, which is a protein kinase that promotes protein synthesis and cell growth."

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"Tumor cells from TSC patients show biallelic activation of TSC1 or TSC2, leading to AKT independent activation of the mTOR signaling pathway."

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"These, in turn, activate other effectors such as the serine threonine kinase AKT, which can activate mTOR, a key regulator of cell growth."

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"AKT can further activate mTOR, which includes mTOR complex 1 (mTORC1) and mTORC2."

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"One such candidate, the rapamycin analog CC1779, which inhibits the potential PKB and Akt target mTOR, is under investigation by several groups [XREF_BIBR]."

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"Akt also targets downstream protein mTOR that has been shown to favor angiogenesis and growth; research into the use of aspirin (mTOR inhibitor) has demonstrated that it inhibits CRC progression."
| PMC

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"Activated AMPK via its downstream effector TSC2 negatively regulates mTOR, leading to apoptosis, while Akt promotes activation of the mTOR pathway [XREF_BIBR, XREF_BIBR]."

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"Inhibition of PI3K and Akt reduced mTOR activity, which effectively enhanced the anticancer effort of an mTOR inhibitor."

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"PI3-kinase and AKT cause an upregulation of p21 by suppressing GSK-3beta activity and activating mTOR in both cultured human urothelial carcinoma cells and mouse urothelial cells in vivo."

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"Estradiol prevented the injury-induced decrease in Akt activation and phosphorylation of mTOR and p70S6 kinases, and the subsequent decrease in S6 phosphorylation."

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"AKT that is phosphorylated on Thr803 by PI3K (phosphatidylinositol 3-kinase) inhibits AMPK and induces mTOR activation."

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"Additionally, Akt activation stimulates the activity of mTOR kinase, which is responsible for substrate switching and suppression of the inflammatory response."

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"In addition, recent preclinical studies have shown that dual inhibition of mTOR with rapamycin and Akt with perifosine prevents mTOR inhibition-initiated Akt activation and significantly enhances antitumor effects in lung cancer [ xref ] and multiple myeloma [ xref ]."

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"Because the binding of insulin to its receptors activates the PI3K and AKT pathway, which is known to stimulate mTOR activity, Kalaany and Sabatini 's observations that tumor cells bearing constitutively activated PI3K mutations are proliferative in vitro in the absence of insulin or IGF-1 and form DR resistant tumors in vivo [XREF_BIBR] clearly suggest that cancer cell-autonomous alterations (e.g., activating mutations of PI3K) may ultimately determine the response of cancer cells to CR, DR, or CRMs."

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"The protein kinase Akt activates mTOR via direct phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2), which is a negative regulator of mTOR xref ."

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"In the present study, the activation of PI3K and its important downstream effector, Akt, which activates mTOR and p70S6K, were detected, showing a marked increase in HSG and inhibition in TSG (XREF_FIG)."

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"MTOR also can be activated by the PI3K and Akt signaling cascade and PI3K and Akt aberration or mutations in various tumor types can be found in the data of The Cancer Genome Atlas (TCGA) consortium s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"At hippocampal CA1 synapses, mGluR5 activation is coupled to protein synthesis XREF_BIBR via PI3K-Akt mammalian target of the rapamycin (mTOR) XREF_BIBR or ERK-MAPK XREF_BIBR signaling pathways."

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"Previous studies have revealed that Akt (protein kinase B, also known as PKB), an important upstream signaling protein of mTOR, activates mTOR, which in turn promotes protein synthesis through the phosphorylation and activation of ribosomal protein S6 kinase (S6K1), and the phosphorylation and inactivation of the mRNA translation repressor, known as eukaryotic initiation factor 4E-binding protein (4E-BP1) [ xref , xref ]."

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"FAK activation leads to the AKT-dependent activation of mTOR, which in turn inhibits autophagy ( xref ; xref )."

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"Akt phosphorylates and activates mTOR, a Ser/Thr kinase with 2 distinct protein complexes, mTORC1 and mTORC2 (for review, see )."

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"PI3K activates AKT, which activates mTOR to prevent cell proliferation and the IκB kinase to initiate NF-κB activity."

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"PI3K is a heterodimer that promotes cellular growth and survival by activating Akt, which subsequently activates the mammalian target of rapamycin (mTOR) [ xref , xref , xref , xref , xref ]."

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"However, in the case of EGFR-mutant H1975 NSCLC cells (L858R and T790M positive), our study suggests that alternative EGFR signaling may be occurring mainly through the MAP Kinase and/or PI3K and Akt stimulated mTOR pathway, resulting in cancer cell proliferation and survival."

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"AKT is known to activate mTOR which exists in two different complexes - mTORC1 and mTORC2."

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"Activation of mTOR by AKT decreases autophagy , and decreased autophagy induces stem cells to differentiate into osteoblasts as well as promotes the calcification of smooth muscle cells.17 , 18 We observed that the mTOR inhibitor rapamycin reduced ALPL gene expression and TNAP activity and prevented calcification of CD73-deficient cells ( Figure 2A-C ) ."

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"Besides this, activation of mTOR by AKT can phosphorylate and inactivate 4E-BP1 (for eIF4E Binding Proteins), a family of small acidic proteins that function as translational repressors of eIF4E."

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"Akt then inhibits tuberous sclerosis complex 2 and activate the mammalian target of rapamycin complex 1 to promote insulin induced adipogenesis."

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"Akt can activate its downstream serine/threonine kinase mammalian target of rapamycin (mTOR), which then phosphorylates p70 ribosomal protein kinase (p70S6K) and 4E-binding protein 1 (4E-BP1), leading to initiation of protein synthesis."

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"Akt gets activated by phosphorylation of its Ser473 residue and stimulates the mTOR complex 1 (mTORC1) by phosphorylating tuberous sclerosis complex2 (TSC2) and subsequently inhibiting TSC1/2 complex formation, which is a negative regulator of mTORC1."

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"AT1 activation leads to Akt independent activation of mTOR, and inactivation of eEF2K, but fails to activate eEF2 and to increase eEF1A expression."

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"In addition, Akt stimulates activation of mTOR."

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"As Akt, which activates mTOR, negatively regulates high oxidative gene expression by inactivating AMPK (see ‘PI3K–AktmTOR pathway’), competitive interaction exists between signaling pathways regulating structural and metabolic protein turnover (Fig.  xref )."

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"The AMPK pathway inhibits mTOR activation [XREF_BIBR], while the PI3K and Akt pathway stimulates the activation of mTOR [XREF_BIBR]."

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"have reported the existence of a protective pathway in cardiomyocytes which involves p38 and Akt mediated mTOR activation in an ischemia and reperfusion model of C75 and B16 mice, while other researchers have postulated an increased phosphorylation of MAPK (e.g. p38) and mTOR in branchial arch muscles from 8- to 26-months-old F344 rats."

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"Consistent with these findings, treatment of primary mouse hepatocytes with the IGF1R inhibitor PPP abrogated AKT dependent activation of mTOR pathway and reduced the expression of lipogenic enzymes (XREF_SUPPLEMENTARY)."

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"PTEN inhibits PI3K dependent activation of AKT, while activated AKT triggers downstream mTOR and p70 S6K1 signaling resulting in the induction of pro angiogenic factors, thereby inducing neovascularization to promote tumor growth."

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"AKT activation inhibits the major inhibitory proteins of the mTOR pathway, tuberous sclerosis 1 and 2 (TSC1/2), resulting in the activation of the mTOR pathway and subsequent inhibition of macroautophagy."

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"The signalling pathway that participates in the transduction of the signal initiated by IGF-1, and was discovered the most recently, is the serine/threonine kinase mTOR pathway, which is also activated by AKT kinase."

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"Additionally, one of the most conserved autophagy pathways is dependent on the metabolic checkpoint kinase mTOR, which can be initiated by AKT."

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"It may be that PTRH2 regulates mTOR through its activation of the FAK-PI3K-AKT pathway because, in the context of cell size, mTOR is activated by way of PI3K and AKT XREF_BIBR - XREF_BIBR."
| PMC

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"These observations suggest that AMPK activation by TAK1 can subdue AKT mediated mTOR activation, leading to decreased ULK1 S757 and S6K1 T389 phosphorylation in S. Typhimurium infected HeLa cells."

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"Akt activates mTOR through direct phosphorylation of the tuberous sclerosis complex 2, which otherwise inhibits mTOR activity ( xref , xref ; xref )."

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"Furthermore, we detected decreased phosphorylation status of Akt, which modulates mTOR signaling."

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"The binding of BDNF to TrkB receptors and/or modulation of NMDA receptors activates AKT, ERK1/2 or PKC; the main activators of the mTOR signaling (Hoeffer and Klann, 2010; Numakawa et al., 2014; Chang[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Although SNRPA1 is one of U2 snRNPs, the role of SNRPA1 in HCC is unclear.Aberrant activation of mTOR signaling is found in approximately half of HCC cases, largely due to alterations of upstream tumor suppressors and oncogenes, including PI3K, AKT, PTEN and TSC1/2 [12]."

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"It has been reported that Akt activates mTOR through phosphorylation and inhibition of the tuberous sclerosis complex (TSC) protein TSC2."

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"MTOR activation is regulated downstream of the class I PI3K- and v-akt murine thymoma viral oncogene homolog (Akt)/protein kinase B (PKB) pathway, and activation of the PI3K-Akt pathway activates mTOR, resulting in suppression of autophagy 22."

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"MTOR is activated by AKT and it stimulates protein translation by phosphorylating eIF4E binding protein (4E-BP1) as well as p70S6K which phosphorylates S6."

sparser
"AKT activates the mTOR complex 1 (mTORC1) to inhibit autophagy."

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"After its binding, AKT can activate mTOR complex (mTORC), leading to protein synthesis and cellular proliferation by stimulating 4E binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1) [XREF_BIBR]."

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"Direct activation of mTOR by AKT was assessed using a phospho-specific antibody directed toward S2448 ( xref ), a phospho-site that correlates with increased mTORC1 activity and up-regulated protein synthesis ( xref ). xref illustrates that mTOR is phosphorylated within 15 min of BDNF stimulation, and this S2448 phosphorylation is blocked by treatment with STO-609."

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"Physiological hypertrophy is initiated by finite signals, which include growth hormones (such as thyroid hormone, insulin, insulin like growth factor 1 and vascular endothelial growth factor) and mechanical forces that converge on a limited number of intracellular signalling pathways (such as PI3K, AKT, AMP activated protein kinase and mTOR) to affect gene transcription, protein translation and metabolism."

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"NF-ĸB signalling is connected to Akt, which can serve to activate the mTOR (mTORC1) pathway; this has been shown to contribute to endochondral growth [21,22,23,24]."
| PMC

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"It has now been well established that Akt is the upstream activator of mTOR."

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"Although it is clear that growth factor induced activation of Akt blocks TSC1 and TSC2 inhibition of mTOR signaling [XREF_BIBR - XREF_BIBR], the molecular mechanism by which Akt inhibits the function of TSC1 and TSC2 protein complex as a cell growth suppressor is still undefined."

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"In addition, Akt phosphorylation results in activation of the mTOR (mammalian target of rapamycin) and raptor complex, which in turn activates downstream mediators including pP70S6K, resulting in regulation of protein synthesis and cell growth."

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"The PTEN and TSC2 tumor suppressors function to antagonize mTOR (mammalian target of rapamycin) activation by Akt; hence, compound heterozygous inactivation of Pten and Tsc2 in the mouse may in principle exacerbate the tumor phenotypes observed in the single mutants in a reciprocal manner."

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"Activation of the PI3K/AKT pathway also increases the activity of the serine/threonine kinase mechanistic target of rapamycin complex 1 (mTORC1) through the phosphorylation and inhibition of the mTORC1 inhibitor TSC; mTORC1 then serves as a major stimu- lant of anabolic metabolism (Liu and Sabatini, 2020; Manning and Toker, 2017; Mossmann et al., 2018)."

reach
"Activated mTOR further phosphorylates ribosomal p70 S6 kinase (S6K1), eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), and Akt, controlling cell proliferation, growth, and survival."

reach
"Consistently, Akt and Erk signaling, which has been proven to activate mTOR pathway, were not inhibited after methylene blue treatment."

reach
"In addition, AKT also activates the mTOR signal directly by inhibiting PRAS40 [XREF_BIBR]."

reach
"found that not only was the PI3K and Akt mediated activation of mTOR 's TORC1 pathway important forTh17 differentiation, but they also attribute its effects to a concerted nuclear trafficking of RORgammat and suppression of Gfi-1, an inhibitor of Th17 differentiation."

reach
"Western blotting analyses showed that silencing of the ATM gene alone had little effect on the level of cleaved PARP in HepG2 cells, but markedly depressed the activation of the Akt mediated mTOR path[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Insulin induces phosphorylation of Akt, which then activates mammalian target of rapamycin complex 1 (mTORC1) via inhibition of TSC1/2, leading to activation of SREBP1c, an adipogenic transcription factor which regulates fatty acid synthase, lipoprotein lipase and PPARγ expression [ xref , xref , xref , xref , xref ]."

reach
"Independent of TSC2, AKT also stimulates mTOR activity directly by inhibiting PRAS40."

sparser
"Phosphorylation and subsequent activation of mTOR by Akt has been shown to promote neurite growth and branching in primary hippocampal neurons [ xref ]."

reach
"Once activated, Akt stimulates the rapamycin sensitive mTOR complex-1 (TORC1) and subsequently S6K, which phosphorylates the ribosomal protein S6."

reach
"PI3K and Akt pathway induces mTOR and also attenuates apoptotic proteins such as GSK3beta and forkhead family of transcription factor."

reach
"Protein kinase B (Akt) and the mitogen activated protein kinase (MAPK) signals activate mTOR through the interaction of tuberous sclerosis complex (TSC) 1/2, v Rheb and the mammalian target of rapamycin complex 1/2 (mTORC1/2)."

reach
"AKT initiates the mTOR pathway, which regulates HIF1A protein biosynthesis by regulating cap dependent translation and ribosome biogenesis."

sparser
"The mTOR kinase is the central player for autophagy induction, with activation of mTOR by Akt and MAPK inhibiting autophagy."

sparser
"Akt activates mTORC 1 via inhibitory phosphorylation of TSC2 , which along with TSC1 , negatively regulates mTORC1 through inhibiting the Rheb GTPase , a positive regulator of mTORC 1."

reach
"On the other hand, activated Akt also stimulates mTOR leading to inhibition of autophagy [XREF_BIBR]."

sparser
"Through intermediate steps, AKT also activates mechanistic target of rapamycin complex 1 (mTORC1) ( xref ), a kinase that is responsible for the initiation of dendritic protein translation, synaptic plasticity, memory processes xref , xref and addiction xref ."

sparser
"Mechanistically, the activation of mTOR and IκB kinase (IKK) by AKT leads to stimulation of NF-κB [ xref ]."

reach
"Interestingly, Akt phosphorylation on Ser473 and Thr308 was not altered (XREF_FIG and D), suggesting that GSK-3beta inactivation and mTOR activation were not mediated by Akt."

sparser
"Akt phosphorylates and activates mTOR, thus inducing protein synthesis and cell growth [ xref , xref ]."

reach
"Similarly, PI3K and AKT activation downstream of the IL-2 receptor can activate mTOR, allowing anergic T cells to upregulate their metabolic output to adapt to the demands raised by activation in otherwise metabolically anergic cells [XREF_BIBR, XREF_BIBR]."

sparser
"After its binding, AKT can activate mTOR complex (mTORC), leading to protein synthesis and cellular proliferation by stimulating 4E binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1) [ xref ]."

reach
"In many cell types, mTOR signalling is predominantly regulated by PI3K and its target Akt, acting on the TSC complex - inhibition of either PI3K or Akt would be predicted to eliminate mTOR activation."

reach
"AKT stimulates mTOR activity by phosphorylating the tuberous sclerosis complex (TSC2) and suppressing its repressive action [XREF_BIBR]."

reach
"MTOR kinase, in complex with the protein Raptor (mTORC1 complex), is indirectly activated by Akt, through phosphorylation of its inhibitor tuberous sclerosis complex [XREF_BIBR]."

eidos
"AKT activates the mTOR ( mammalian target of rapamycin ) pathway , which increases cyclin D1 translation to promote cell cycle progression62 , and stimulates CREB activity to induce survival genes such as Bcl-263 ."

reach
"This increase in AKT activity attenuated the effect of mTOR inhibition and facilitated cancer cell growth and survival."

reach
"It has been reported that the phosphorylation of Akt induces the activation of mTOR and reduces the activation of GSK3beta [XREF_BIBR, XREF_BIBR]."

reach
"Alternatively, the mTOR kinase can be activated by Akt independently of TSC 1/2 and can be regulated by MAPKs."

reach
"PI3K and AKT signaling, in turn, activates mTOR, which has been associated with various diseases, including cancers XREF_BIBR."

reach
"Hyper-active Ras, Raf, Akt not only can arrest cycle but additionally activate the mTOR pathway."

reach
"XREF_BIBR, XREF_BIBR Since activation of the PI3K and AKT cascade promotes mTOR activity, many tumor types exhibit high levels of mTOR activity due to constitutive upstream signaling events."

reach
"The PI3K and Akt signaling pathway positively regulate the mTOR pathway to promote actin reorganization in seminiferous epithelium."

reach
"As reported, USP14 was activated by AKT,32 so the non‐effect of mTOR activator on SPAG5 indicated that it was AKT, rather than mTOR that activated USP14 and led to upregulation of SPAG5 level in HG‐treated HPCs."

reach
"Activation of Akt and ERK1/2, which are required for lasting and fast antidepressant effects XREF_BIBR, stimulate 4E-BP1 or p70S6K activation in an mTOR dependent or mTOR independent manner."

sparser
"Akt activates mammalian target of rapamycin (mTOR) which promotes protein synthesis through activation of p70 ribosomal S6 kinase (p70S6K), and the inhibition of eIF4E binding protein (eIF4EBP) [ xref , xref ]."

sparser
"PTEN regulates the pathway by inhibiting the phosphorylation of AKT, which activates mTOR when phosphorylated [ xref ]."

sparser
"AKT phosphorylates and activates mTOR kinase, leading to the phosphorylation/activation of anti-apoptotic protein Mcl-1 ( xref , xref )."

sparser
"In the PI3K/AKT/mTOR signaling pathway, AKT activates mTOR, thereby accelerating the transcription of genes required for cell cycle progression through the regulation of the downstream targets, 4EBP1 and p70S6K ( xref – xref )."

sparser
"Activation of mammalian target of rapamycin complex 1 by Akt resulted in increased protein translation of DNMT3a."

reach
"Our results show that suppression of KCa3.1 with siRNA gene silencing blocked TGF-beta1-induced activation of PI3K, Akt and downstream signaling of mTOR, which led to the induction of autophagy in HK2 cells."

reach
"The increased phosphorylations of PI3K, AKT, and mTOR, and the upregulation of CXCL8 induced by miR-204 suppression were all abolished by the addition of LY294002 and AZD8055 (inhibitors of PI3K and AKT and mTOR, respectively)."

reach
"The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that is often hyperactivated in cancer, and stimulation of both Akt and ERK1/2 can lead to activation of a protein complex containing mTOR, i.e., mTORC1."

reach
"Similarly, expression of ZIKV-NS4A and/or ZIKV-NS4B inhibits AKT phosphorylation, reduces mTOR signaling, and induces autophagy in human neural progenitors (XREF_FIG)."

reach
"Subsequently, activated PI3K or Akt may positively regulate mTOR, leading to increased phosphorylation of ribosomal p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), the two best characterized downstream effector molecules of mTOR [XREF_BIBR - XREF_BIBR]."

reach
"Our study revealed that TBP-2 's impact on LECs under oxidative stress is independent of the activation of mTOR by Akt."

reach
"Interestingly, both the mTORC1 inhibitor rapamycin (100 nmol/L) and the AMPK inducer AICAR decreased the BCAA‐induced activation of Akt and mTORC1 (Figure 1D,E) suggesting that in response to BCAA, AMPK is likely activated to counteract the Akt/mTOR pathways and that there is a reciprocal relationship between mTORC1 and Akt."

reach
"The PI3K phosphorylates phosphatidylinositol-4,5-bisphosphate to produce PI3P that induces Akt phosphorylation, which activates mTOR and results in the inhibition of autophagy in GC cells (21)."

reach
"Indeed, overexpression of AKT, which activates mTOR, results in hypermyelination as a result of an increased number of myelin wraps [XREF_BIBR]."

reach
"According to this model, mTOR would be activated by PKB."

reach
"We demonstrate that FAK is recruited to SCVs in a manner that is dependent upon the SPI-2 T3SS, where it promotes robust Akt activation and stimulation of the mTOR signaling pathway."

reach
"Activated AKT is a tumorigenic driver in ganglioneuroma, and inhibition of the downstream AKT target mTOR may serve as a means to shrink large ganglioneuromas prior to resection in order to reduce surgical morbidity."

sparser
"The UA-induced NF-κB activation in skin melanoma cells was relatively sustained in response to mTOR inhibition, suggesting that both AKT and the AKT-activated mTOR exert regulatory effects on PGC-1α expression."

reach
"Although a large body of evidence demonstrates that AKT activates mTOR in numerous cell types [XREF_BIBR], Finlay et al. have shown that mTOR can also be regulated by PDK1 (and not AKT) in CD8 + T cells [XREF_BIBR]."

reach
"Akt mediated activation of mTOR complex 1 (mTORC1) then causes increased cellular proliferation by phosphorylating proteins such as p70 S6 kinase (S6K) and 4E binding protein 1 (4E-BP1) that regulate protein synthesis [XREF_BIBR]."

reach
"ERK1/2- and Akt mediated mTOR signal transmission was activated by ketamine, showing rapid antidepressant effects."

reach
"Akt is then able to activate mammalian target of rapamycin (mTOR), which is a regulator of protein synthesis and cell survival (Memmott and Dennis, 2009)."

reach
"Akt induction also triggered activation of mTOR and p70 S6K cascade, a pathway known to contribute to cell growth and survival XREF_BIBR, XREF_BIBR."

reach
"We have previously shown that induction of AKT activity by vGPCR promotes mTOR activation in neighboring cells XREF_BIBR."

reach
"Combined inhibition and knockdown of Akt 1 to 3 failed to block mTOR activation despite inhibiting Tsc2 (XREF_FIG), arguing against Tsc2 as a critical intermediate."

reach
"MTOR is activated by Akt, a downstream product of phosphatidylinositol 3-kinase (PI3K), whereas the major negative regulator of mTOR is 5 ' AMP activated protein kinase (AMPK), which regulates intracellular energy status by sensing the AMP and ATP ratio [XREF_BIBR - XREF_BIBR]."

sparser
"Akt further activates mTOR complex 1 (mTORC1), which functions as a nutrient sensor and initiator of protein and ribosome synthesis ( xref )."

sparser
"Akt subsequently activates the mammalian target of rapamycin (mTOR) and S6 kinase (S6K), which is involved in protein synthesis and cell growth."

reach
"FTY720 induced inhibition of PI3K and Akt pathway downregulated mTOR signalling, which was shown to be crucial for FTY720 mediated inhibition of migration and invasion of glioblastoma cells [XREF_BIBR]."

reach
"The overactivation of PI3K and AKT signaling triggers the activation of the mTOR (mammalian target of rapamycin)-pathway."

reach
"MTOR can be activated by several stimuli such as growth factors, nutrients through receptor tyrosine kinase (RTK), phosphatidyl inositol 3 kinase (PI3K), and Akt and PKB signaling cascade [13]."

reach
"Additionally, Akt can activate mTOR, which results in stimulation of protein synthesis and cell growth [XREF_BIBR]."

sparser
"Unlike Drink, Cereal had a significant effect on mTOR and Akt phosphorylation (Figure xref ), implying that mTOR was activated by Akt and also by the amino acids in the nonfat milk."

reach
"Akt activates mTOR complex 1 (mTORC1), which contains mTOR and regulatory associated protein of mTOR (Raptor), via inhibition of tuberous sclerosis protein (TSC) 2."

reach
"MTOR and pS6 were inhibited by Akt inhibition (p < 0.05), but activated after stimulation with PDGF (p < 0.01 and p < 0.001 respectively)."

reach
"Furthermore, we have also identified a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt independent signaling route stimulating mTOR."

reach
"TGF-beta-mediated PI3K and AKT signaling may further induce activation of mTOR and subsequent fibrosis related gene expressions [XREF_BIBR]."

reach
"Further results indicated that PI3K and AKT pathway mediated inhibition of the mammalian target of rapamycin (mTOR) pathway played a role in the activation of autophagy by resveratrol after CIH stimulation."

reach
"Down-regulation of AKT and PI3K leads to inactivated mTOR and induce autophagy in cancer cells [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

reach
"Akt/protein kinase B (PKB) lies upstream of mTOR, so activated Akt may positively regulate mTOR, leading to increased phosphorylation of ribosomal p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), two best characterized downstream effector molecules of mTOR [23]."

reach
"AKT activates the mTOR (mammalian target of rapamycin) pathway, which increases cyclin D1 translation to promote cell cycle progression , and stimulates CREB activity to induce survival genes such as Bcl-2 ."

reach
"A key effector of AKT induced signaling is the regulatory protein mTOR."

sparser
"In contrast, AKT phosphorylates and activates mTOR to suppress autophagy xref ."

reach
"The serine/threonine kinase mTOR is a well‐characterized substrate of Akt and it is known that Akt‐mediated activation of mTOR occurs through phosphorylation and inactivation of tuberous sclerosis complex 2 (TSC2), which normally inhibits mTOR (Hay 2005)."

sparser
"The regulation of mTOR by the LKB1/AMPK signal functionally and mechanistically parallels that of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) signal where AKT activates mTOR via TSC2. xref Similar to LKB1, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), the negative regulator of PI3K/AKT, functions as a tumor suppressor in a plethora of cancer types."

trips
"However, the mechanism by which Akt activates mTOR is not fully understood."

reach
"In its active form, Akt activates mTOR complex 1 (mTOR, Raptor and GbetaL), leading to phosphorylation of 4EBP1 and p70S6K to promote protein translation 12."

reach
"AkT can positively regulate mTOR activation directly through phosphorylation at Ser 2448."

reach
"In addition, we hypothesize that galangin and pinocembrin may have a synergistic effect via Akt and mTOR signaling pathway, while galangin and pinocembrin upregulate the phosphorylation of IR, Akt, and GSK3beta, downregulate the phosphorylation of IRS, and activate Akt and mTOR pathway."

reach
"AKT, protein kinase B alpha; ER, endoplasmic reticulum; IKKβ, I-kappa-B kinase beta; IKKɛ, I-kappa-B kinase epsilon; IRS1/2, insulin receptor substrate 1; ISRE, interferon-stimulated response element; MAVS, mitochondrial antiviral signaling protein; mTOR, mechanistic target of rapamycin; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PI-3K, phosphoinositide-3-kinase; STAT1/2/3/4/5/6, signal transducer and activator of transcription 1/2/2/4/5/6; STING, stimulator of interferon genes; TBK1, TANK-binding kinase 1.Fig."

reach
"In a separate study, DOX was also shown to inhibit AMPK protein expression and phosphorylation in the rat heart through DNA damage induced Akt signalling, which activates mTOR signalling in a negative feedback loop and leads to cardiac remodelling [XREF_BIBR]."

reach
"Consistently, the PI3K and mTOR targets Akt and S6 appeared to be intrinsically phosphorylated (i.e. activated) and fully sensitive to SOM230 treatment in CAFs while not constitutively activated and hence not inhibited by SOM230 in PaSCs (Fig XREF_FIG)."

reach
"Activation of growth factor receptors, Ras, Raf, PI3K, Akt, which all activate mTOR, are most common alterations in cancer [XREF_BIBR - XREF_BIBR]."

reach
"MTOR is activated by AKT and it stimulates protein translation by phosphorylating eIF4E binding protein (4E-BP1) as well as p70S6K which phosphorylates S6."

sparser
"Akt can directly phosphorylate and activate mTOR and also inhibit mTOR inhibitor proteins proline-rich Akt substrate of 40 kDa (PRAS40) and tuberin (TSC2)."

sparser
"AKT, in turn, activates the downstream kinase mTOR, which stimulates p70 S6 kinase and other effectors, ultimately culminating in enhanced protein synthesis [ xref - xref ]."

reach
"Nevertheless, while Bradley et al. found that HDAC inhibitor repressed mTOR activity could be rescued by overexpression of constitutively active Akt, PT effectively inhibited mTOR even in cells expressing constitutively active Akt (XREF_FIG)."

reach
"Increasing evidences suggested that mTOR can be activated by Akt signaling pathway in gastric cancer [XREF_BIBR, XREF_BIBR]."

reach
"PtdIns (3,4,5) P 3 in turn recruits both phosphatidylinositol dependent kinase 1 (PDK1) and AKT and PKB to the membrane where PDK1 phosphorylates and activates AKT and PKB and indirectly activates the mTOR."

reach
"Although this mechanism may enhance mTOR activation, it does not fully explain how Akt activates mTOR."

reach
"It remains to be seen how PKB might signal to mTOR and how this modest increase in mTOR activity results in the large increase in the phosphorylation state of effector molecules, such as 4E-BP1."

reach
"Akt also activates mTOR, a key regulator of cell growth and proliferation that integrates signaling from insulin and growth factors, amino acid availability, cellular energy status and oxygen levels [XREF_BIBR, XREF_BIBR]."

reach
"The primary regulator of protein synthesis in skeletal muscle is the activation of mammalian target of rapamycin (mTOR), which is activated by Akt via insulin or insulin like growth factor 1 (IGF1) and mechanical stimuli."

sparser
"Another is AKT-dependent activation of the mTOR complex 1 (mTORC1) and the downstream serine/threonine kinase p70 S6 kinase 1 (S6K1)."

reach
"The GLP-1RAs not only prevent JNK/IKK activation, but promote insulin activation by PI3K/AKT axis, with the subsequent activation of mTOR and the block of GSK-3β, an essential kinase also involved for the phosphorylation of tau protein (Moloney et al., 2010)."

sparser
"Akt then activates the downstream protein mammalian target of rapamycin (mTOR), which phosphorylates translation initiation through ribosomal p70S6 kinase (p70S6k) or eukaryotic translation initiation factor 4E (eIF4E) binding proteins (4E-BPs)."

reach
"These results suggested that cyst fluid TNFalpha might act through PI3K-Akt mediated activation of mTOR to increase the levels of Id2 to regulate cyst lining epithelial cell proliferation during cyst development, which might be one of the reasons that rapamycin could inhibit cyst lining epithelial cell proliferation in Pkd1 knockout mouse models [XREF_BIBR]."

reach
"Expression and/or activation of the mitogen activated protein kinase MAPK (RAS/RAF/ERKs) and phosphatidylinositol 3-kinases (PI3Ks)/protein kinase B (PKB-AKT)/mammalian target of rapamycin kinase (mTOR) pathways are abnormally high in many HCC cells, which render the latter resistant to apoptotic stimuli XREF_BIBR - XREF_BIBR."

sparser
"PI3K and Akt are upstream of mTORC1 and activate mTOR to inhibit autophagy ( xref )."

reach
"The data shown in Figure 4 therefore collectively suggest that the major factor responsible for the PDGF induced activation of Akt is the activation of the PI 3-kinase."

reach
"XREF_BIBR Akt activates mTOR through direct phosphorylation at Ser 2448, resulting in the activation of mRNA translational machinery."

reach
"In addition, activated Akt can stimulate the mTOR pathway [XREF_BIBR]."

reach
"Knocking down AMPK and overexpressing Akt increased mTOR activity and attenuated DHA induced cell death, suggesting that DHA induces cell death via AMPK- and Akt regulated mTOR inactivation."

reach
"Further experiments indicated that the AKT signaling pathway was inhibited in the HG + 2% FBS group; however, miR-328 downregulation activated the AKT and mTOR signaling pathway, which was blocked by the AKT signaling pathway inhibitor, perifosine."

reach
"Suppression of AKT decreases mTOR activity and promotes autophagy 43."

reach
"AKT positively regulates mTOR (activator of PGC-1alpha) by direct inhibition of the inhibitory complex TSC1/2 and by inhibition of the mTOR inhibitors AMPK (activator of PGC-1alpha) and GSK3b (regulator of PGC-1alpha turnover) [XREF_BIBR, XREF_BIBR]."

reach
"AKT can also activate mTOR independently of TSC2, via PRAS40 (AKT1S1; proline rich AKT-substrate 40 kDa)."

sparser
"Constitutively active Ras, PI3K, and Akt that activate the mTOR kinase induce growth and elaboration of dendrites in cultured hippocampal neurons."

reach
"We demonstrated that resistance to AZD1208 occurs through feedback activation of mTOR signaling, which is mediated by ROS, p38, and AKT."

sparser
"The mechanistic target of rapamycin (mTOR), the most widely studied negative regulator of autophagy, is usually activated by PI3K-Akt and directly inhibits ULK1 to inhibit autophagy ( xref )."

reach
"MTOR receives signaling from multiple pathways including Akt dependent and AKT independent mechanisms, in which mitogenic signals, energy, nutrients and so on generally functions as an initiators to activate the mTOR signaling [XREF_BIBR]."

sparser
"Akt activates mTOR via phosphorylation and inactivation of tuberous sclerosis complex (TSC)-2."

sparser
"Various members of this PKC family have been implicated in progression of cell cycle, apoptosis and differentiation. xref Protein kinase A family of proteins is activated in response to G coupled protein receptors xref while PRKCD plays a key role in autophagy suppression which is achieved by the process of phosphorylation of AKT which further activates mTOR, specific for fibrolamellar carcinoma. xref In current study, activity of c-SRC decreases with progressive liver fibrogenesis and hepatic stellate cell (HSC) activation."

reach
"The activation of regulators such as growth factors receptor recruits PI3K to the cell membrane and phosphorylates AKT which later induces mTOR activation leading to the activation of its downstream effectors (4EBP1 and P70S6) and eventually induces RNA translation, protein synthesis, cell survival, and so on [18] ."

reach
"AKT activation could activate downstream of mTOR, thereby inhibiting autophagy [12]."

reach
"For instance, the activation of mTOR by Akt culminates in the activation of NF-kappaB, which is associated with inhibitor of NF-kappaB kinase (IKK) and mTORC1 complex 's Raptor [XREF_BIBR] (XREF_FIG)."

sparser
"Although it is not clear precisely how Akt may activate mTOR, recent evidence suggests the tuberous sclerosis complex, an autosomally dominant tumor suppressor complex involved in the tuberous sclero[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"33 Furthermore, phosphorylation of IRS-1 downstream Akt (Ser473) signalling causes mTOR activation by phosphorylation at Ser2448."

reach
"Inhibition of tyrosine phosphatase activity (3,4-dephostatin) blocked the synergy between MNTX and temsirolimus and increased VEGF induced tyrosine phosphorylation of Src with enhanced PI3 kinase and mTOR Complex 2 dependent phosphorylation of Akt and subsequent activation of mTOR Complex 1 (rapamycin and temsirolimus target), while silencing Src, Akt or mTOR complex 2 components blocked VEGF induced angiogenic events."

reach
"XREF_BIBR - XREF_BIBR Once activated, AKT can target downstream modulators of apoptosis such as GSK3beta, IRS-1 (insulin receptor substrate-1), PDE-3B (phosphodiesterase-3B), BAD, caspase-9, Forkhead proteins, NF-kappaB, mTOR, nitric oxide synthase (NOS), Raf protein kinase, and BRCA1."

reach
"Of interest, direct and paracrine AKT activation of the TSC2 and mTOR pathway has been shown to be necessary and sufficient for vGPCR oncogenesis."

reach
"Since activation of the PI3K and Akt cascade promotes mTOR activity, this pathway is an important regulator of cellular autophagy."

reach
"20 mTOR activation by Akt contributes to regulation of de novo lipogenesis."

reach
"Phosphoinositide 3-kinase (PI3K), pyruvate dehydrogenase kinase (PDK), and protein kinase B (PKB; Akt) activation induced by growth factors (GFs) activate the mammalian target of the rapamycin (mechanistic target of rapamycin kinase; mTOR) pathway, which results in elevated HIF-1α transcriptional activity [6]."
| PMC

reach
"XREF_BIBR, XREF_BIBR CK2 activates Akt, XREF_BIBR, XREF_BIBR and the activation of Akt and mTOR signaling inhibits Treg differentiation and induces effector T cell differentiation."

reach
"TGF-beta-mediated PI3K and AKT signaling may further induce activation of mTOR and subsequent fibrosis related gene expressions [139]."

reach
"In the organotypic culture model of post-traumatic epileptogenesis, mTOR activation was mediated by PI3K-Akt pathway suggesting that growth factor signaling may be involved XREF_BIBR."

eidos
"Akt activates mTOR by regulating the cellular ATP level and AMPK activity [ 34 ] ."

sparser
"Akt indirectly activates mTOR, a complicated checkpoint of cellular growth influenced by growth factor signaling, adenosine monophosphate levels, and nutrient and O 2 availability. xref mTOR refers to 2 distinct multimolecular complexes, mTOR complex 1 (mTORC1) and complex 2 (mTORC2)."

sparser
"As a downstream effector of PI3K, Akt is involved in regulation of various signaling pathways involved in cell metabolism, proliferation, survival, growth, and angiogenesis. xref Akt can activate mTOR at Ser2448, which plays a key role in cell growth, autophagic cell death, and homeostasis. xref PTEN is a negative regulator of PI3K and inhibits Akt/mTOR and MAPK signaling, leading to inhibition of cell growth and cell death. xref The results show that danusertib inhibited activation of Akt at Ser473 without a significant change in expression of total Akt in either cell line ( xref )."

reach
"MTOR is activated by AKT and regulates cell survival, migration, and proliferation XREF_BIBR."

reach
"Pharmacological inhibitors of PI3K, AKT, PLC and rapamycin all abrogate polyP induced mTOR signaling in both in vitro and in vivo models."

reach
"This coordination of IGF-1 and AKT and mTOR pathways enables the activation of mTOR, which in turn promotes cell growth in response to the stimulation of growth factors, including insulin and IGF-1 (XREF_FIG)."

sparser
"Activation of PI3K-AKT leads to increased phosphorylation of AKT, which activates mTOR and this, in turn, phosphorylates the ribosomal protein S6 in human cancers ( xref )."

sparser
"Subsequently pAkt activates mTOR to enhance HIF-1α transactivation activity, HIF-1α/HIF-1β bind to the HRE of VEGF promoter region to induce VEGF production, then 33-kDa ANXA3 promoted angiogenesis of HepG2 cells through activating PI3K/Akt via increasing HIF-1α expression; (3) Furthermore, pAkt decreases Bax and increases Bcl-2 expressions, Bax upregulation and Bcl-2 downregulation promoted cytochrome c release from mitochondria into the cytoplasm, then binds to Apaf-1 and forms apoptosome to recruits and activates pro-caspase 9, following by pro-caspase 3 cleavage and activation, cleaved-caspase 9 and cleaved-caspase 3 blocked DNA damage repair to induce apoptosis, then 33-kDa ANXA3 inhibited HepG2 cells apoptosis and chemoresistance via activating caspase 9 and caspase 3."

reach
"Consistently, an increased phosphorylation of the Akt targets mTOR Ser2448 and GSK3beta Ser9 is observed, confirming the occurrence of an anomalous Akt activation induced by imatinib-resistance."

reach
"However, in response to high level of ATP, Akt activates mTOR through inhibition of AMPK mediated phosphorylation of TSC2 on T1227 and S1345 [XREF_BIBR]."

reach
"The PI3K and AKT signaling pathway activates mTOR activity in response to growth factors, and this and previous studies [XREF_BIBR] have shown that PI3K and AKT and mTOR signaling are key growth pathways underlying organ regenerative growth in the Burmese python."

eidos
"Therefore , loss of PTEN function leads to an increase of Akt activity , which in turn triggers mTOR activity , thus stimulating cell proliferation and survival [ 42,43,44 ] ."
| PMC

reach
"Akt modulates mTOR activity by direct phosphorylation of a complex known as tuberous sclerosis (TSC1 and TSC2), which has been established as the major upstream inhibitory regulator of mTOR [20]."

reach
"Based on our data, PIM or AKT inhibition can downregulate mTOR in some DLBCL cell lines."

reach
"Our results agree with those from previous studies [XREF_BIBR, XREF_BIBR] and indicate that the inhibition of AMPK and the activation of AKT synergistically activate mTOR in islets from GC treated mice and rats, which may corroborate the increased GSIS and beta-cell mass."

sparser
"AKT indirectly activates mTOR, which plays similar functions of ERK, thereby eventually activating HIF-1 signaling pathway (Richardson et al., xref )."

reach
"Being the central node of the PI3K network, AKT activates the mechanistic target of rapamycin kinase complex 1 (MTORC1) via Tuberous sclerosis complex 2 inhibition in the cytoplasm."

reach
"Subsequently, activated PI3K or Akt may positively regulate mTOR, leading to increased phosphorylation of S6K1 and 4E-BP1 [XREF_BIBR]."

reach
"The activated PI3K and Akt may further activate its downstream molecule mTOR through the TSC1/2 complex, and the activated mTOR can activate its two downstream molecules subsequently, which are the translation inhibitory molecule eIF-4E binding protein 1 (4E-BP1) and ribosomal protein p70S6K."

sparser
"IGF-1 induces the phosphorylation of Akt which then activates mTOR and its downstream targets p70S6k and 4E-BP to initiate protein translation and synthesis xref , xref ."

reach
"In addition, mutant PIK3CA in HPV associated tumors correlated with activation of downstream mTOR, but not Akt pathway."

sparser
"The combined results suggest that GA-induced autophagy is associated with Akt protein degradation via a mechanism that is dependent on Hsp90 inhibition and on inhibition of Akt activation of mTOR."

eidos
"Through inhibition of tuberous sclerosis protein 2 ( TSC2 ) , the AKT also activates mTOR which functions as serine / threonine protein kinase regulating cell growth , survival , protein synthesis and autophagy [ 66 ] ."

sparser
"PI3K activation leads to phosphorylation and activation of AKT, which in turn can activate downstream mTOR."

reach
"Phosphorylation of PI3K and Akt activates mTOR, a serine/threonine kinase."

reach
"Co-expressed in fetal neural stem cells, ZIKV non-structural proteins NS4A and NS4B decreased AKT phosphorylation and subsequently inhibited mTOR activation, which induced autophagy95 (Fig. 3)."

eidos
"AKT also activates Mammalian target of rapamycin ( mTOR ) protein kinase , a serine / threonine kinase by phosphorylation [ 62,63,64 ] ."

reach
"First, we measured mTOR activity in cells transduced with CA-STAT5 or an AKT variant known to trigger mTOR signaling (CA-AKT) (30)."

reach
"While this finding was not unexpected, as plasma amino acid levels were dramatically decreased in these mice and branched-chain amino acids are known stimulators of insulin release XREF_BIBR, our finding that the phosphorylation of Akt was unchanged in response to dietary protein intake indicates that insulin and Akt does not mediate the observed changes in mTOR activity."

reach
"18 The proteins phosphatidylinositol 3-kinase (PI3K) and Akt are important activators of mTOR."

reach
"Indeed, IGF-1 treatment is sufficient to cause muscle hypertrophy via Akt activation of mTOR and inhibition of GSK3beta."

reach
"First, as mTOR acts downstream of Akt and Akt is known to positively regulate mTOR, inhibition of Akt by ML-9 could consequently induce mTOR inhibition and activation of autophagy."

reach
"Both PI3K-I and Akt and MAPK/Erk1/2 signaling activate mTOR which then suppress autophagy, while AMPK and p53 signaling inhibit mTOR thereby promoting autophagy [XREF_BIBR]."

reach
"Akt signaling activates the mTOR pathway via phosphorylation of tuberous sclerosis protein 2 (TSC2), thereby repressing its inhibitory activity on mTOR complex 1 (mTORC1) assembly XREF_BIBR."

sparser
"In β-thalassemia, Akt in turn activates the mammalian target of rapamycin (mTOR), blocking autophagic processes with the accumulation of damaged proteins such as the highly pro-oxidant free-alpha globin chains."

reach
"AKT phosphorylation as a predictive biomarker for PI3K/mTOR dual inhibition-induced proteolytic cleavage of mTOR companion proteins in small cell lung cancer."

sparser
"These data are consistent with a model in which activated Akt in turn activates mTOR, which inhibits expression of Mirk."

reach
"Oppositely, phosphorylation of AKT and downstream activation of mTOR seem quite essential for pro-cancer progression function of ADORA1 in HCC from both in vitro and in vivo data of the current study."

sparser
"Akt activates mTOR by relieving proline-rich Akt substrate 40 (PRAS40)-mediated inhibition of mTOR."

sparser
"For instance, the activation of mTOR by Akt played an important role in cell proliferation, survival, and growth [ xref ]."
| PMC

reach
"Activation of mTOR signaling by Akt and PKB involves the phosphorylation and inactivation of TSC2 [XREF_BIBR]."

reach
"Paradoxically, despite Akt being a known activator of mTOR, we found that HMA treatment promoted an increase in the mTORC1 substrate phospho-S6 kinase and decrease in Akt."

reach
"This finding could be explained by Akt only indirectly activating mTOR in the canonical PI3K/Akt/mTORC1/P70S6K pathway, and this activation may be tissue specific [XREF_BIBR, XREF_BIBR]."

sparser
"Moreover, AKT can also activate mammalian target of rapamycin (mTOR), which stimulates protein synthesis and cell growth."

reach
"Activation of the PI3K and Akt pathway negatively regulates autophagy by targeting the downstream mTOR complex."

sparser
"It has also been shown that Akt activation of mTOR leads to increased regeneration following axotomy [ xref ]."

sparser
"Therefore, it may be speculated that AKT activates mTOR when RSK-3 is inhibited and serves as a potential compensatory mechanism to maintain the CSPC proliferative capacity."

sparser
"The delicate process of starvation-induced autophagy xref is inversely regulated by mTOR which is activated by PI3K-Akt induced by insulin or other growth factor xref , xref ."

reach
"Akt activates the downstream mTOR signaling pathway."

reach
"Generally, the upstream signal PI3K and AKT or nutrients activate mTOR thus suppressing autophagy."

sparser
"Additional phosphorylation at Ser473 leads to full AKT activation and phosphorylation of mTOR at Ser2448 leads to full activation of the mTOR protein."

reach
"Previous evidence suggests that stimulation with insulin like growth factor leads to mTOR activation mediated by P13K and AKT signals to inhibit autophagy."

reach
"Mechanistically, the activation of mTOR and IkappaB kinase (IKK) by AKT leads to stimulation of NF-kappaB [XREF_BIBR]."

reach
"For example, oncogenic Ras, Raf-1, B-Raf, MEK, Akt and PI3K activate the mTOR pathway, but (by inducing p21 WAF1/CIP1/SDI1, p27 KIP1, p16 Ink4A and p53) can cause cycle arrest leading to cell senescen[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"A broad range of upstream signals, including growth factors, hormones and cytokines, provoke the activation of PI3K that phosphorylates and thereby activates AKT, which is the upstream activator of mTOR."

reach
"HC toxin induced Akt activation was sufficient to enhance downstream mTOR complex 1 (mTORC1) signalling including p70S6K and S6, which were consistently abolished by PI3K inhibition."

sparser
"AKT activates the mammalian target of rapamycin (mTOR), a key cellular regulator of mitosis, survival, and increased cellular size."

reach
"AKT activates mTOR by phosphorylation at serine 2,448 to improve the efficiency of mRNA translation, increase the expression of a series of cell proliferation and differentiation associated proteins, and promote tumor development and progression."

reach
"The down modulation of mTOR by androgen deprivation and androgen deprivation plus IL-6 treatment indicates that the mTOR pathway is not targeted by PI3K-Akt but rather is controlled via a negative regulatory pathway."

reach
"In fact, it has been reported that SIRT1 deacetylates AKT, which binds to phosphatidylinositol (3,4,5)-triphosphate, leading to the activation of the AKT/mTOR pathway."

sparser
"AKT also activates the mechanistic target of rapamycin (mTOR) and induces cellular senescence (Johnson, Rabinovitch, & Kaeberlein, xref )."

sparser
"AKT can activate mTOR at least through two distinct mechanisms: directly by phosphorylation at the S2448 site or indirectly by inhibition of the tuberous sclerosis complex 2 (TSC2)."

sparser
"We show that Salmonella -induced FAK activation leads to the Akt-dependent activation of mTOR, thereby repressing autophagic signaling."

sparser
"In addition Akt also activates mTOR, whose signaling is closely related to the presence of soluble amyloid beta (Aβ) and tau protein."

reach
"A PI3K or Akt specific inhibitor prevented morphine induced increases in the phosphorylated forms of 4E-BP1, mTOR, and S6K1 in the spinal cord."

reach
"Mechanistically, HFD suppressed autophagosome biogenesis through AMPK- and AKT-mediated mTOR activation and decreased ATG7, resulting in KEAP1 stabilization and decreased NRF2 levels in mouse liver."

reach
"Akt directly and indirectly activates mammalian target of rapamycin (mTOR) signaling by enhancing its downstream molecules, including eukaryotic initiation factor 4E-binding protein (4E-BP1) and ribosomal protein S6 kinase (S6K), and promoting cell differentiation, growth, and survival (Martelli et al., 2010; Sabbah et al., 2011)."

reach
"88 AKT further activates mTOR, which is also responsible for integrating cellular signals regarding nutrient levels, cellular energy stores, and stress."

reach
"It has been demonstrated that PI3K/AKT can activate its downstream factors mTOR and Nrf2 (Kim et al., 2013), which are involved in axon branching, autophagy, alleviating oxidative damage, and down-regulating tau protein phosphorylation as well as apoptosis of neurons via inhibiting caspase 3 and glycogen synthase kinase (GSK) -3β (Chami et al., 2016)."

reach
"The lower mTOR activation in the 19R group than in the 19S group, even on the isocaloric and isoprotein diets, may be the result of insulin deficiency that decreased Akt (an activator of mTOR) [XREF_BIBR] phosphorylation and activated PTEN in the 19R group compared to the 19S group."

reach
"AMOG mediated Akt phosphorylation specifically activates the mTOR and p70S6 kinase pathway previously implicated in cell size regulation, but it does not depend on tuberous sclerosis complex and Ras homolog enriched in brain (Rheb) signaling."

reach
"92 Akt directly and indirectly leads to activation of mTOR which is present in two distinct complexes : mTORC1 and mTORC2."

reach
"Temsirolimus is an inhibitor of Akt pathway that targets mTOR protein and undergoes a phase II trial in individuals with relapsed or refractory NB (NCT01767194)."

reach
"XREF_BIBR, XREF_BIBR As PI3K and Akt triggers downstream signals to mTOR for cellular growth and proliferation, the loss of miR-126 and miR-199a-3p could facilitate tumor growth."

reach
"In the presence of glucose, AKT also promotes MCL-1 protein synthesis by stimulating mTOR mediated protein translation."

reach
"Next, we examined whether Akt directly activates mTOR pathway signaling by a downstream protein of the mTOR, 4E‐BP1."

reach
"Both mTOR and S6K1 activities may be stimulated by Akt kinase."

reach
"MET triggers the activation of PI3K and AKT, which increases mTOR activation, which in turn inhibits p53 (by promoting the translation of Mdm2)."

reach
"Signalling mTOR protein is activated by the Pi3K and AKT cascade and provides the signal which regulates both mRNA translation and cell growth."

sparser
"AKT can also activate mTOR independently of TSC2, via PRAS40 (AKT1S1; proline-rich AKT-substrate 40 kDa)."

reach
"Akt activates mTOR by inhibiting tuberous sclerosis complex 2 (TSC2), which heterodimerizes with TSC1, thereby inactivating Rheb and mTOR."

reach
"While the PI3K-mTOR pathway was inhibited by serum deprivation, dopamine increased the phosphorylation of Akt but inhibited mTOR activity in a similar way to rapamycin."

reach
"Akt, in turn, can activate mTOR by direct phosphorylation and indirectly through inhibition of the tumor and suppressor complex, composed of TSC1 and TSC2."

reach
"The mTOR is activated by PI3K-AKT signaling [27], and mTOR expression was also reduced by TrkB and TrkC knockdown treatment."

reach
"In CML cells, however, the autophagic process is suppressed by multiple mechanisms, including AKT mediated mTOR activation 14 and BCR-ABL-induced Beclin 1 phosphorylation, 15 and is implicated in cell survival and TKI resistance."

reach
"The increased phosphorylations of PI3K, AKT and mTOR, and the up-regulation of CXCL8 induced by miR-204 suppression were all abolished by addition of LY294002 and AZD8055 (inhibitors of PI3K and AKT and mTOR, respectively)."

reach
"We found that BTV1 induced a marked reduction in Akt and mTOR activity as well as a great increase in LC3-II, especially at 36hpi (XREF_FIG), implying that Akt positively regulates mTOR."

reach
"Autophagy is regulated by several cellular signaling pathways, class I phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB)-mammalian target of rapamycin complex 1 (mTORC1), and other mTOR independent pathways, for instance, cyclical Ca 2+ -calpain-Galphas and cAMP-Epac-PLC-epsilon-IP3 and the basic helix-loop-helix leucine zipper transcription factor EB (TFEB)-mediated pathway [XREF_BIBR] (XREF_FIG)."

reach
"AKT can activate mTOR at least through two distinct mechanisms : directly by phosphorylation at the S2448 site or indirectly by inhibition of the tuberous sclerosis complex 2 (TSC2)."

reach
"AKT activation of downstream mTOR kinase signaling promotes cell growth."

sparser
"Akt can directly phosphorylate and activate mTOR, as well as indirectly activating it by phosphorylating and inactivate tuberous sclerosis complex 2 (TSC2), also called tuberin, which normally inhibits mTOR through the GTP binding protein Ras homolog enriched in brain (Rheb) [ xref ]."

sparser
"PAkt activated mTOR to enhance HIF-1 transactivation activity and induce VEGF production xref ."

reach
"In summary, full understanding of the molecular mechanisms, signaling pathways, and the secondary causes of muscle and/or fat wasting are essential for successful CC management.Table 1: List of therapeutic agents and factors available for the management of cancer cachexia.Figure 1: The common assessment for the clinical management of cancer cachexia.Figure 2: Molecular mechanisms regulated by IGF-1 and MSTN: Active Akt produces the mTOR signal, which leads to protein synthesis and inhibits (phosphorylates) FoxO."

reach
"Oxidative stress induced cellular senescence stimulates the PI3K and AKT pathway, subsequently suppressing forkhead box O (FoxO) transcriptional factors and elevated mammalian target of rapamycin (mTOR) [XREF_BIBR]."

reach
"Akt, a serine/threonine kinase, can activate mTOR and p70 S6 kinase (S6K)."

sparser
"AKT activates MTOR by a cascade of phosphorylations, and MTOR inhibits autophagy through the inhibitory phosphorylation of ULK1 (unc-51 like autophagy activating kinase 1) and ATG13, proteins required for autophagy induction. xref GSK3 has recently been shown to be part of this regulatory cascade."

reach
"Although Akt has many downstream targets, Akt mediated mTOR activation is one of the main determinants in transcriptional regulation."

reach
"For class I PI3K, the proliferation signal is induced by the PI (3,4,5) P3 mediated activation of AKT, which in turn enhances mTOR activity."

reach
"We then analyzed the activities of Akt kinase and AMPK kinase, two major kinases controlling mTOR activity : The Akt kinase mediates the activation of mTOR in response to growth factors, and the AMPK kinase is involved in mTOR activity inhibition in response to nutritional, genotoxic and metabolic stress signals [XREF_BIBR, XREF_BIBR]."

reach
"As expected, NVP-BEZ235 simultaneously blocked Akt phosphorylation and mTOR activation in all three RCC cell lines, while PP242 directly inhibited mTOR activity and subsequently prevented activation of Akt."

sparser
"PI3K activation activates Akt which activates mTOR."

reach
"Moreover, the activation of mTOR mediated by AKT suppresses GC autophagy during follicular atresia XREF_BIBR."

eidos
"PI3K activates protein kinase B ( PKB ) , also known as AKT , which in turn activates mTOR ."

reach
"Moreover, the PLCgamma pathway has no effect on Stat5 activation, but directly controls AKT independent activation of mTOR."

reach
"Consistent with what has been reported in the literature, mTOR inhibition was potentiated by inhibitors of PI3K and AKT and MEK derived from the screened chemical library."

reach
"These data indicate that Akt dependent activation of mTOR cascade is a major oncogenic event in E2F1 overexpressing livers."

sparser
"The tumor suppressor TSC2 (tuberous sclerosis 2) is phosphorylated by Akt, which activates the mTOR kinase [ xref ]."

reach
"RAS and ERK and PI3K and AKT both stimulate the serine/threonine kinase mTOR, thereby promoting phosphorylation of mTOR substrates, which then promote growth and cell-cycle progression."

reach
"Fully activated AKT leads to mTOR activation and the subsequent inhibition of autophagy."

reach
"In this review, we summarize ErbB receptor signaling, PDGF receptors, MAP kinase signaling, AKT, p21 activated kinase signaling, mTOR, and VEGF signaling in the context of vestibular schwannoma drug development efforts worldwide."

reach
"Akt can phosphorylate to activate mTOR, which is present in two distinct protein complexes : mTORC1 and mTORC2."

reach
"XREF_BIBR, XREF_BIBR AKT also promotes the activation of mTOR which supports neuronal differentiation and growth by increasing protein synthesis, pyrimidine synthesis, and preventing autophagy."

reach
"Here we tested whether subversion of AKT mediated mTOR activation in S. Typhimurium infected HeLa cells was due to TAK1 activated AMPK."

reach
"It has been shown that PI3KC1 phosphorylates protein kinase B/Akt and that Akt induces activation of mTOR, which regulates several cellular functions such as cell growth, proliferation, and autophagy."

eidos
"Suppression of mTOR signaling by the expression of a dominant negative mutant of the Akt kinase cause an increase in Bcl-2 phosphorylation in HEK23 human embryonic kidney cells [ 45 ] , suggesting that Akt inactivation may inhibit mTOR expression and upregulate Bcl-2 phosphorylation , thereby preventing cell apoptosis ."

reach
"Canonically, mTOR is activated by PKB/Akt [17,18]."

sparser
"Activated AKT phosphorylates and activates mTOR and inhibits FOXO."

reach
"Because wortmannin reduced VEGF-C or -D induced LDC proliferation (see Supplemental Figure S1A at http://ajp.amjpathol.org), we investigated whether PI3K and Akt dependent activation of mTOR was invol[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"As a result, PI3K and Akt is activated and stimulates mTOR."

reach
"MTOR is a positive regulator for cell cycle progression and cellular proliferation, and is activated by AKT via phosphorylation of mTOR at Ser2448."

reach
"AKT also effectively activates the mTOR pathway and regulates protein synthesis by phosphorylating the p70 ribosomal protein S6 kinase (AGC Ser/Thr protein kinase family)."

reach
"Liu et al. showed that activation of the PI3K and AKT pathway could result in activation of mTOR and the proliferation of endometrial cells by inhibiting autophagy [XREF_BIBR]."

sparser
"Growth factors like IGF-1 bind to insulin-like growth factor receptors (IGF1Rs), activating AKT which subsequently activates mTOR [ xref ]."

sparser
"PI3K inhibition in the ovarian cells resulted in inhibition of Akt phosphorylation, a major downstream target of PI3K. Akt activates mTOR through a variety of cellular mechanisms, and thus regulates apoptosis-associated proteins [ xref ]."

reach
"The mTOR and receptor complex is activated by Akt and phosphorylase S6 Kinase, which has been reported to cause insulin resistance by serine phosphorylation of insulin receptor substrate-1 (IRS-1), eventually disrupting PI3K-Akt signaling [XREF_BIBR]."

reach
"Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo."

reach
"This interaction causes the activation of PKB and Akt, which in turn induces the mTOR pathway implicated in the stimulation of protein synthesis [XREF_BIBR]."

reach
"Co-expressed in fetal neural stem cells, ZIKV non-structural proteins NS4A and NS4B decreased AKT phosphorylation and subsequently inhibited mTOR activation, which induced autophagy 95 (FIg."

sparser
"Akt will then activate mTOR through ribosomal protein S6 kinase (RPS6KB1) and by phosphorylating and inhibiting tuberous sclerosis complex (TSC), which originally inhibits mTOR [ xref ]."

reach
"The activation of PI3K and Akt stimulates mTOR, which encourages cells to restrain autophagy activation followed by cell death [XREF_BIBR]."

reach
"Activation of mTOR by AKT and MAPK signaling suppresses autophagy signaling, while mTOR inhibition by the negative regulators AMPK and p53 drives the process forward."

reach
"Indirect activation of mTOR by Akt initiates the activation of pro translational signaling by the activation p70 S6 Kinase (p70 S6K) and the deactivation of 4E Binding Protein (4E-BP) through phosphorylation."

reach
"Murphy et al. (42) found that connexin 43 can induce resistance to temozolomide by activating the AKT/AMP-activated protein kinase/mammalian target of rapamycin signaling pathway in malignant gliomas."

reach
"AKT activates mTOR to become phosphorylated mTOR (p-mTOR) through TSC1/2."

reach
"Phosphatidylinositol 3 kinase (PI3K) can be activated in response to growth factors and several hematopoietic cytokines leading to the activation of downstream kinases such as the serine/threonine kinase Akt (also known as protein kinase B or PKB) that, in turn, can activate the mTOR (mammalian target of rapamycin) complex."

sparser
"Once phosphorylated, Akt can indirectly activate the mammalian target of rapamycin or mTORC1 complex."

reach
"Moreover, by inhibition of tuberous sclerosis protein 2 (TSC2), AKT activates mammalian target of rapamycin (mTOR) [XREF_BIBR, XREF_BIBR]."

sparser
"In a well-fed state, insulin signaling is activated and AKT phosphorylates and activates MTOR."

sparser
"This reduction was mediated by AKT-dependent activation of mTOR complex 1, which in turn induced the differential translation of the dominant-negative C/EBPβ isoform, liver inhibitory protein (LIP)."

reach
"Cardiac PI3K and Akt causes insulin stimulated glucose absorption and produces acute mTOR activation, thus improving the cardiomyocytes ' survival and function."

reach
"Because Pten is a negative regulator of the PI3K-AKT pathway, which in turn stimulates mTOR by inactivating the TSC complex, it is likely that the inactivation of TSC1 is at least in part responsible for Pten induced hyperproliferation of HSCs."

reach
"Finally, we show that activation of mTOR and p70S6K can still occur despite reductions in Akt, suggesting the existence of an Akt independent mechanism that activates mTOR and p70S6K in myoblasts."

sparser
"In the present study, the activation of PI3K and its important downstream effector, Akt, which activates mTOR and p70S6K, were detected, showing a marked increase in HSG and inhibition in TSG ( xref )."

reach
"Akt, on the other hand, activates mTOR by destabilizing TSC1 (Tuberous sclerosis 1) via phosphorylation [82]."

reach
"This second messenger recruits Akt, which promotes mTOR activity."

reach
"AKT activates mTOR through TSC1/2 leading to protein synthesis and cell growth [XREF_BIBR]."

reach
"The mTOR cascade is also activated by Akt leading to enhanced cell growth and protein production but also EMT [XREF_BIBR]."

reach
"The key signaling molecule PKB and Akt positively regulates mTOR by phosphorylating and inactivating TSC2 and by phosphorylating and activating mTOR directly."

reach
"These observations suggest that S. Typhimurium can subvert AKT mediated mTOR activation, and that blocking of mTOR activity may contribute to Salmonella induced autophagy."

reach
"AKT and PI3K pathway activation is common in EOC/PPC, resulting in constitutive activation of downstream mTOR."

eidos
"The interaction between Ca2 + signalling , PKA and mTOR signalling has been postulated by several groups , where PKA phosphorylates Akt / PKB , which in turn activates mTOR [ [ 45 ] , [ 46 ] , [ 47 ] , [ 48 ] , [ 49 ] ] ."

reach
"The significance and function of the AKT independent activation of the mTOR complexes in the context of tumor dormancy remain to be elucidated, but it exemplifies the complex molecular interactions often observed in the study of tumor dormancy."

sparser
"Phosphorylated AKT further activates mTOR, thereby activating protein translation, promoting cell proliferation ( xref )."

reach
"The AKT target mTOR was also inhibited as shown by a decrease in mTOR phosphorylation at serine 2448 followed by P70S6K downregulation."

reach
"PI3K is a heterodimer that promotes cellular growth and survival by activating Akt, which subsequently activates the mammalian target of rapamycin (mTOR) [24,25,26,27,28]."

reach
"XREF_BIBR Insulin, for example, is important for glucose availability, but also for autophagy regulation due to the PI 3-kinase and AKT mediated activation of MTOR."

reach
"Taken together, our findings indicated that AKT mediated activation of mTOR suppresses granulosa cell autophagy during follicular development and is involved in the regulation of apoptotic cell death."

reach
"Activated PI3K phosphorylates AKT, which in turn activates IKKA, MTOR (FRAP1) and MDM2 and inhibits FKHR, CASP9, BAD, p27 and p21 genes [XREF_BIBR - XREF_BIBR]."

reach
"The mammalian class I PI3K and its product PI (3,4,5) P3 block autophagy by activating Akt and PKB, which activates mTOR (mammalian target of rapamycin) kinase, the principal negative regulator of autophagy."

reach
"TC21 induced transformation and proliferation required activation of p38 MAPK, mTOR (the mammalian target of rapamycin), and phosphoinositide 3-kinase but not Akt and PKB."

reach
"The elimination of PTEN activity (by mutation, deletion or epigenetic silencing) can lead to oncogenesis through activation of Akt, which in turn upregulates mTOR activity."

reach
"Moreover, Akt induced activation of mTOR, enables mRNA translation through the activation of P70S6 kinase and the inhibition of 4E-BP1, a translational repressor of mRNAs."

sparser
"PI3K triggers Akt which consequently activates mTOR."

eidos
"Under physiological conditions , growth factors and cytokines activate tuberous sclerosis 1 proteins 1 and 2 by activating PI3K and phosphorylating Akt , which then activates mTOR ."

reach
"Subsequently, activated PI3K or Akt may positively regulate mTOR, leading to increased phosphorylation of S6K1 and 4E-BP1, the two best characterized downstream effector molecules of mTOR [XREF_BIBR - XREF_BIBR]."

sparser
"Akt further activates mTOR through the tuberous sclerosis complex (TSC)."

reach
"AKT then promotes activation of mTOR - a protein, which exists as two complexes; mTORC1 and mTORC2."

reach
"Subsequently, it was reported [XREF_BIBR] that DIM could inactivate both mammalian target of rapamycin (mTOR) and Akt activity in PDGF-D-over-expressing prostate cancer cells, PC3."

reach
"Mammalian target of rapamycin (mTOR) signaling, downstream of PI3K-AKT signaling activation, could be activated by phosphorylation of AKT to regulate autophagy process via mTOR-Atg1-Atg13 or mTOR-ULK1-Atg13 signal transduction under pressure stimulation or oxidative stress stimulation [33]."

reach
"BTV1 infection induces the suppression of Akt and upregulation of AMPK via [Ca2+]cyto-mediated CaMKKβ activation, leading to the TSC2-mediated inhibition of mTOR and downstream p70S6K, ultimately leading to autophagy initiation."

reach
"The results showed that NL-101 reduced the phosphorylation of Akt and mTOR (Figure 5(b)), suggesting that NL-101 can induce autophagy by inhibiting Akt/mTOR signaling pathway."

sparser
"Increased glycolysis and ATP production is the predominant pathway by which AKT activates mTOR and tumorigenesis [ xref ]."

sparser
"Akt directly phosphorylates and activates mTOR [ xref ]."

reach
"However, AKT mediated mTOR activation can occur through a variety of mechanisms, including direct mTOR activation [XREF_BIBR], phosphorylation of the proline rich in AKT substrate of 40 kDa (PRAS40) [XREF_BIBR], or through inactivation of the tuberous sclerosis complex (TSC) [XREF_BIBR]."

reach
"Therefore, in response to growth factors such as insulin, the PI3K-Akt pathway activates mTOR signaling through phosphorylation and inhibition of tuberin (XREF_FIG A)."

eidos
"AKT activates mammalian target of rapamycin ( mTOR ) ."

reach
"From these, it is inferred that PKC delta and PI3K and Akt might activate mTOR and p70S6K in an experimental asthma model."

reach
"Moreover, the Akt signal pathway positively regulates mTOR, which has been associated with bad prognosis and earlier recurrence in tumor treatment."

reach
"The western blotting results suggested that H/R stimulation decreased PI3K, AKT and mTOR phosphorylation, and significantly decreased the ratios of p-PI3K and PI3K, p-AKT and AKT and p-mTOR and mTOR compared with the control group."

reach
"ATF6alpha provides a cell survival response through the up-regulation of Rheb and Akt independent activation of mTOR."

reach
"With regard to the effect of ALC on this pathway, we propose that the disruption in IGF-1-induced Akt phosphorylation caused by the drug may lower mTOR signaling, resulting in a decrease in KiSS-1 gene expression."

reach
"Normally, RAS, RAF, MEK1/2, and ERK indirectly stimulate AKT activation of mTOR via inhibition of TSC1/2."

sparser
"Activated AKT (or p-AKT) could further activate mTOR by phosphorylation, which could regulate cell stress response and cell cycle. xref As PTEN mutations are seen early in endometrioid ovarian carcinoma and endometrioid ovarian cancer is thought to arise from EMs, it has been proposed that somatic genetic alterations in the PTEN gene may be an early event in MTOE. xref The ovarian endometrioid adenocarcinoma with an activated PI3K–AKTmTOR signaling pathway is more likely to be of a low grade instead of a high grade. xref In our present research, PTEN expression was progressively reduced in the order of EMs, atypical EMs, and malignant EMs."

sparser
"Akt activates mTOR either directly by phosphorylating it at Ser 2448 or indirectly by inhibiting the tumor suppressor activity of tuberous sclerosis complex (TSC1/TSC2) through phosphorylation of TSC2 [ xref , xref ]."

sparser
"Rapamycin and AKT inhibitor uniformly abrogated mTOR inhibition-induced AKT activation but failed to induce antitumor responses in a subset of head and neck cancers ex vivo xref ."

reach
"Welker et al previously indicated that, through the PI3K/AKT/mTOR signaling pathway, activated AKT activates mTOR and regulates two downstream factors, consisting of eukaryotic initiation factor 4E binding protein 1 and ribosomal S6 protein kinase 1, in addition to controlling the translation of proteins for cell proliferation and transformation."

reach
"Presumably, the suppression of Akt expression induced a much far greater suppression of the Akt and mTOR pathway by RAP administration in MSTN-pro mice than in wild-type mice."

reach
"The finding that mTOR was activated both via phosphorylation by Akt and through inactivation of the mTOR inhibitor, TSC2, implies a selective pressure toward mTOR activation in E2F1 and c-Myc and E2F1-driven hepatocarcinogenesis."

sparser
"PI3K can activate AKT, which in turn can activate mTOR, an important pathway in cell survival ( xref )."

reach
"MTOR is a central modulator of the initiation of protein translation 3 and is activated by Akt, also known as protein kinase B, from the phosphoinositide-3 kinase signal cascade."

reach
"This could be due to other types of alterations in PIK3CA that we were not able to detect or to alterations in other components in the PI3K/AKT pathway that activate mTOR."

reach
"Our belief of radiation induced cyclical deregulation is further strengthened by the fact that there is increased PI3K and Akt signaling invariably linked to increased ROS production as well as Akt mediated activation of mTOR, which is known to downregulate autophagy (XREF_FIG)."

reach
"Akt promotes cell proliferation and survival by inactivating proapoptotic substrates such as procaspase-9, Bad and Foxo-3alpha and activating NF-kappaB and mTOR, which control proliferation, oncogenesis and ribogenesis."

reach
"The PI3K and AKT pathway activates mTOR signaling, a major regulator of glucose metabolic pathways in the cell."

sparser
"This component recruits the AKT (protein kinase B), which subsequently activates MTOR (mechanistic target of rapamycin kinase) by phosphorylation [ xref ]."

reach
"Akt phosphorylation, in turn, results in the activation of mTOR 31 and the existence of an mTOR dependent signaling mechanism for maintaining pluripotency and suppressing differentiation of hESCs by inhibition of the Wnt signaling pathway has been recently reported 32."

sparser
"In addition to GSK-3β, PI3K-Akt also activates mTOR, thereby potentiating Snail1 expression in gastric, breast, pancreatic and ovarian cancer ( xref – xref )."

sparser
"Akt activates mTOR through (i) phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2), which inactivates the mTOR-activating GTP-binding protein Rheb, and/or (ii) phosphorylation of PRAS40 a member of mTORC1, one of the two functional complexes of mTOR, which includes mLST8/Gbl and the scaffold protein Raptor ( xref )."

reach
"Similarly, inhibiting Akt, which mediates mTOR activation by beta-glucan, or HIF1alpha, a mTOR target and master regulator of glycolysis, attenuated macrophage training."

reach
"The RAF and MAPK and PI3K and AKT pathways both activate mTOR signalling, a process found to be highly regulated in neurofibromas whereby mTOR pathway activation occurs in the absence of growth factors, in both NF1 tumours and neurofibromin deficient cultured cells."

reach
"Investigations on PI3K and AKT signaling found that PI3K and AKT inhibition leads to suppressed activation of its downstream signals mTOR, p70S6K, and 4E-BP1 [XREF_BIBR]."

reach
"AKT indirectly activates mTOR, which plays similar functions of ERK, thereby eventually activating HIF-1 signaling pathway."

sparser
"Akt activates mTOR by regulating the cellular ATP level and AMPK activity [ xref ]."

reach
"TC21 induced transformation and proliferation required activation of p38 MAPK, mTOR (the mammalian target of rapamycin), and phosphoinositide 3-kinase but not Akt and PKB."

sparser
"As phosphorylated Akt activates mTOR and its downstream target p70S6K, we also observed the expression of p-mTOR (78.3%, 48.1%) and p-p70S6K (76.1%, 54.1%) according to the expectation."

reach
"It is well known that a decrease in Akt activity inhibits the mTOR and p70S6K pathway."

reach
"Therefore, based on the present results and the fact that mTOR is activated by Akt, we suggest that the IGF-1 induction of Akt results in the downstream activation of the mTOR signaling pathway and ultimately, the prepubertal stimulation of the KiSS-1 gene."

sparser
"To evaluate whether mTOR was activated by Akt, the phosphorylation level of mTOR was determined by Western blotting."

reach
"17 AKT and PI3K signaling activates mTOR and its downstream effector molecule pp70s6kinase."

reach
"MTOR is activated by the PI3K and Akt signaling pathway, which is downstream of a number of growth factor receptors as well as TLRs, and we have previously reported that this signaling axis is critically involved in orchestrating the metabolic demands necessary for DC activation."

sparser
"Although PI3K activation might decrease SKP2 transcription, and through PKB inactivate TSC2 and activate mTOR, the effects of this pathway on p27 stability are clearly dependent on cell type [ xref ]."

reach
"The protein kinase Akt activates mTOR via direct phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2), which is a negative regulator of mTOR XREF_BIBR."

reach
"The PI3K/AKT/mTORC1 pathway plays a key role in promoting cell survival and proliferation.35 Downstream of PI3K activation, phosphorylation and activation of AKT leads to activation of mTOR to regulate a number of cellular processes."

reach
"PI3K can activate AKT, which in turn can activate mTOR, an important pathway in cell survival."

reach
"Using biochemical and genetic approaches, the kinases IKKi and GSK3alpha were identified as the critical intermediate signaling components for IL-1-induced AKT activation, which in turn activated mTOR."

reach
"Via a cascade: PI3K activation phosphorylates Akt, which activates mTOR."

sparser
"These results suggest a model in which CD28 ligation in the presence of TCR signaling activates NFκB through PI3K. Akt also activates mammalian target of rapamycin (mTOR) resulting in increased cell cycle activity and glucose metabolism ( xref – xref )."

sparser
"Previous studies have demonstrated that RAS suppressed cMYC-induced apoptosis via activating PI3K/AKT pathway. xref Activated AKT in turn phosphorylates and activates mammalian target of rapamycin (mTOR), an essential component of mTORC1 that promotes tumor cell proliferation and survival. xref In cMYC/KRAS12V-transduced plasmacytoma cells, genes in mTOR target gene set xref were significantly upregulated ( xref and xref )."

reach
"The PI3K and Akt pathway can also induce mTOR activation."

reach
"In a panel of non small cell lung cancer cells, the compound also attenuated mTOR downstream signaling, including the phosphorylation of p70S6K, S6, and Akt, resulting in G1 cell-cycle arrest and growth inhibition."

reach
"In the PI3K pathway, PKB can also stimulate the mammalian target of rapamycin (mTOR), resulting in the activation of STAT3 [28]."
| PMC

sparser
"Akt activates mTOR by direct phosphorylation, which induces transcription factors associated with growth and cell survival, as well as factors regulating translation initiation, hypoxia, and angiogenesis [ xref ]."

reach
"AKT activates mTOR by phosphorylating tuberous sclerosis complex 1, a negative regulator of mTOR signaling."

reach
"Constitutively active Ras, PI3K, and Akt that activate the mTOR kinase induce growth and elaboration of dendrites in cultured hippocampal neurons."

reach
"After the loss of AMPK activity, AKT is able to activate mTOR and HIF1 XREF_BIBR."

reach
"Akt inhibition decreases mTOR activity and promotes autophagy."

sparser
"Pharmacological inhibition and short hairpin RNA-mediated knockdown experiments showed that AKT-dependent mammalian target of rapamycin (mTOR) activation was involved in the phosphorylation of serine-727 of STAT3, which in turn stimulated the transcription of the CCR1 gene."

reach
"However, preclinical data suggests that AKT inhibition can potentiate the anti-tumor efficacy of mTOR inhibition."

reach
"MTOR activation by Akt or MAPK signaling inhibits autophagy whereas mTOR inhibition by AMPK or p53 signaling enhances autophagy."

reach
"Akt signaling stimulates mTOR within this complex to directly phosphorylate the ribosomal S6 kinases, S6K1 and S6K2, and the eIF4E binding proteins, 4EBP1 and 4EBP2."

sparser
"According to this model, mTOR would be activated by PKB."

reach
"DC120 induced activation of hVps34 leads to the increased production of PIP3 from phosphatidylinositol-3,4-bisphosphate (PIP2) that recruits AKT to plasma membrane again to activate AKT and mTOR signaling by feedback."

sparser
"In this respect, we in this study showed that a low expression of RSK-3 did not sufficiently activate rpS6, despite a potential compensatory activation of mTOR by AKT, and thus inhibited CSPC proliferation."

sparser
"The known pathway by which Akt activates mTOR is via direct phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2), which is a negative regulator of mTOR."

reach
"Conversely, mTOR activating oncogene products such as class I PI3K and Akt inhibit autophagy."

sparser
"Earlier studies showed that mTOR activated by Akt leads to the activation of the pathways that promote protein synthesis and the inactivation of glycogen synthase [ xref , xref ]."

reach
"As protein synthesis in skeletal muscle cells is regulated by Akt and mTOR [XREF_BIBR, XREF_BIBR], we analyzed levels of Akt and p70s6k (a downstream target of mTOR) in control, empty vector, and ICAM-1+ cells through 6 d of differentiation, as well as in ICAM-1+ cells treated with ICAM-1 peptide at 5 d of differentiation."

reach
"MTOR pathway is activated by Akt which can activate NF-kB pathway [XREF_BIBR]."

reach
"The classical signaling pathways for regulating mammalian autophagy relates to the serine/threonine kinase mTOR, which is mainly mediated by PI3K and Akt and MAPK/Erk1/2 signaling transduction [XREF_BIBR]."

reach
"The combined results suggest that GA induced autophagy is associated with Akt protein degradation via a mechanism that is dependent on Hsp90 inhibition and on inhibition of Akt activation of mTOR."

reach
"IL-6-induced AKT phosphorylation activates mTOR that consequently activates its downstream targets p70S6 kinase (p70S6K), 40S ribosomal protein S6 (S6RP) and the eukaryotic initiation factor 4E binding protein-1 (4EBP1), that control mRNA translation and protein synthesis [XREF_BIBR]."

sparser
"It has been reported that the transformation of this metabolic process is regulated by a variety of signaling pathways: Akt can directly upregulate the enzymes in the glycolysis pathway or activate mTOR in downstream to enhance glycolysis xref ."

reach
"We also show that Nef could induce the activation of Akt, which activates mTOR leading to autophagy inhibition."

sparser
"Activated Akt subsequently phosphorylates and activates nuclear mTOR and downstream genes."

reach
"Meanwhile, it is known that Akt causes mTOR activation through a variety of mechanisms 15."

reach
"To confirm whether kindlin-2 induces autophagy via the AKT and mTOR pathway, kindlin-2-overexpressing CaSki cells were treated with the AKT activator SC79 (20 microM) and then autophagy marker expression was assessed."

sparser
"This is achieved through Akt-dependent phosphorylation and inhibition of p21 (Thr 145 ) and downregulation of p27, which relieves the G 1 checkpoint xref – xref and Chk1 inhibitory phosphorylation (Ser 280 ), inhibiting G 2 /M cell cycle arrest. xref Akt activates mTOR through direct phosphorylation at Ser 2448 , resulting in the activation of mRNA translational machinery. xref Akt also stabilizes the caspase-3 inhibitor X-linked inhibitor of apoptosis protein (XIAP) by phosphorylating Ser 87 , preventing XIAP auto-ubiquitination and subsequent proteasomal degradation. xref Akt regulates p53 protein stability and activation through phosphorylation of MDM2 on Ser 166 and Ser 186 , facilitating its nuclear translocation and thereby enhancing p53 ubiquitination and proteasomal degradation. xref , xref "

sparser
"A second pathway regulating eIF4F is PI3 kinase, which activates Akt, which activates mTOR."

reach
"The UA induced NF-kappaB activation in skin melanoma cells was relatively sustained in response to mTOR inhibition, suggesting that both AKT and the AKT activated mTOR exert regulatory effects on PGC-1alpha expression."

reach
"Akt also activates mTOR, which then inhibits RTK signaling in a complex manner that includes phosphorylation and degradation of IRS1 and IRS2, and phosphorylation and stabilization of the PI3K inhibitory protein Grb10."

reach
"The protein expression and activity of mTOR-pathway signaling components, Akt, AMP activated protein kinase alpha, mTOR, p70S6kinase1 and insulin receptor substrate-1 were analysed via western blotting in IUGR v. matched appropriate-for-gestational age (AGA) placentas."

reach
"XREF_BIBR - XREF_BIBR Here we show that activation of the PI3K and AKT pathway would result in activation of mTOR and promote cell proliferation by inhibiting autophagy."

reach
"Increased Akt expression will lead to mTOR activation and increased efficiency of protein translation."

reach
"The serine/threonine kinase mTOR, which is mainly mediated by PI3K and Akt signaling transduction, can negatively regulate autophagy."

sparser
"Akt activates mTOR by phosphorylating and inactivating the mTOR inhibitor, TSC2 ( Krymskaya, 2003 )."

reach
"Moreover, inhibition of Akt reversed the mTOR activation but failed to affect p38 phosphorylation triggered by α-Syn."

sparser
"It is known that PI3K activation leads to the phosphorylation and activation of Akt, which in turn activates mTOR in both mTORC1 and mTORC2 complexes ( xref )."

reach
"The phosphorylation of Akt activates its substrate, rapamycin target protein (mTOR), either directly by phosphorylating mTOR or indirectly by inactivating tuberous sclerosis complex 2 (TSC2) [47], to maintain Rheb's GTP binding state and then enhance the activation of mTOR [48]."

reach
"Akt activation stimulates mTOR, which controls a large number of components related to initiation and elongation [XREF_BIBR]."

reach
"FAK activation leads to the AKT dependent activation of mTOR, which in turn inhibits autophagy."

reach
"Activation of Akt upon PTEN depletion triggers mTOR pathway, which is sufficient to raise beta-actin and axonal growth in MNs."

reach
"The IGF1 pathway, which signals through AKT-mediated activation of mTOR and repression of FOXO, and via the Ras/MAP kinase pathway, is a major regulator of muscle growth and glucose homeostasis (Schiaffino and Mammucari, 2011; O’Neill et al., 2015)."

reach
"Akt activates mTOR by direct phosphorylation, which induces transcription factors associated with growth and cell survival, as well as factors regulating translation initiation, hypoxia, and angiogenesis [XREF_BIBR]."

reach
"Since TSC inhibits the mammalian target of rapamycin (mTOR) through inactivation of the small GTPase Rheb [XREF_BIBR, XREF_BIBR], Akt normally promotes mTOR activity."

sparser
"PI3K activates protein kinase B (PKB), also known as AKT, which in turn activates mTOR."

reach
"Reduced active AKT leads to decreased activity of mTOR and its downstream target, p70s6Kinase, which resulted in the inhibition of cell proliferation."

reach
"Akt also stimulates mTOR to activate pNrf, a prime transcription factor for upregulation of mitochondrial proteins of oxidative phosphorylation."

sparser
"PI3K phosphorylates Akt, which in turn activates mTor complexes to induce cell migration ( xref )."

reach
"Downstream, Akt activates mTOR complex 1 (mTORC1) at mTOR via the tuberous sclerosis complex (TSC)."

reach
"On the other hand, any increase in AKT activity will up-regulate mTOR, which activates NF-κB (164)."

reach
"Phosphorylation of PI3K/AKT leads to activation of mTOR, which is known to regulate the transcriptional factor SREBP1c and control lipogenesis [93]."
| PMC

sparser
"p70S6k activation by Akt is mediated via the indirect activation of mTOR by Akt."

reach
"The interaction between Ca2+ signalling, PKA and mTOR signalling has been postulated by several groups, where PKA phosphorylates Akt/PKB, which in turn activates mTOR [[45], [46], [47], [48], [49]]."

reach
"In this study, we observed that autophagy was excessively activated during the early stage of I/R, and bFGF treatment stimulated phosphorylation of PI3K and Akt and further enhanced mTOR signaling (XREF_FIG and XREF_FIG), resulting in autophagy inhibition."

reach
"Akt mediated activation of mTOR results in activation of p70S6K, which phosphorylates IRS-1 resulting in inhibition of IRS1."

reach
"AKT indirectly activates mTOR, a complicated checkpoint of cellular growth influenced by growth factor signaling, adenosine monophosphate levels, and nutrient and O2 availability [XREF_BIBR]."

sparser
"Akt, a serine/threonine kinase, can activate mTOR and p70 S6 kinase (S6K)."

reach
"Conversely, AKT may be activating alternative pathways instead of mTOR such as activation of IkappaB kinase, a positive regulator of NF-kappaB that transcribes anti-apoptotic genes [XREF_BIBR, XREF_BIBR] or possibly mTOR is activated by AKT independent mechanisms in NPE and PSCC such as via the RAS/MEK/ERK pathway, nutrient starvation and hypoxia, among others [XREF_BIBR]."

sparser
"Akt phosphorylates and activates mTOR, thus inducing protein synthesis and cell growth [ xref , xref ]."

reach
"Finally, CPA6 knockdown enhanced Akt/mTOR phosphorylation and activation, while CPA6 overexpression inhibited Akt/mTOR activation."

reach
"The mammalian class I PI3K and its product PI (3,4,5) P3 block autophagy by activating Akt and PKB, which activates mTOR (mammalian target of rapamycin) kinase, the principal negative regulator of autophagy."

reach
"When PI3K is activated, it triggers AKT phosphorylation, which in turn leads to mTOR activation [5,20,22,31,72,73,[77], [78], [79],84]."

reach
"AKT, in turn, activates PtdIns-3ps, and mTOR [XREF_BIBR]."

reach
"As large amounts of glutamate are released during status epilepticus, a rational mechanism might start with stimulation of ionotropic or metabolic glutamate receptors and subsequent activation of the PI3K and Akt pathway, which in turn can increase mTOR activity (XREF_FIG)."

reach
"Akt is known to activate mTOR leading to the activation of p70S6K, a mitogen activated kinase responsible for the phosphorylation of the S6 protein of the 40S ribosomal subunit, and involved in the translational control of ribosomal proteins and elongation factors XREF_BIBR."

eidos
"Activation of AKT promotes mTOR activity by suppressing the repressive action of tuberous sclerosis complex ( TSC ) through phosphorylation of TSC2 at serine residue 939 and binding of 14-3-3 protein [ 34 ] ."

reach
"This suggests that MSTN may play an important role in LIPUS improving the T1DM induced muscle atrophy by the Akt independent increase in mTOR and inhibition of FoxO1."

sparser
"Akt then activates mTOR, which integrates several upstream signals into effector actions on multiple downstream targets involved in cell growth and division ( xref )."

reach
"Current models suggest that Akt positively regulates mTOR and p70S6K action by acting on mTOR-inhibitory molecules PRAS40 and TSC2, and previous work from our laboratory has established that PI3K p110alpha is the primary PI3K catalytic isoform involved in IGF-I-stimulated Akt activation in C2C12 cells (Matheny and Adamo, manuscript in press)."

sparser
"AKT is a serine/threonine kinase also known as protein kinase B (PKB) which activates mTOR, thereby playing multifaceted roles in the cellular metabolism, proliferation, inflammation, transcription and protein synthesis [ xref , xref , xref ]."

reach
"The mTOR pathway is directly activated by AKT [XREF_BIBR] and suppressed by LKB1-AMPK signaling [XREF_BIBR]."

reach
"AKT acts as a proto-oncogene and mediates mTOR activation, which is common in BC leads to tumor progression, resistance and survival [3]."

sparser
"GSK-3β is a constitutively activated protein inhibited following Akt activation, while mTOR is activated by Akt [ 44 , 45 ]."

reach
"Proliferation and persistence of T H 17 cells following IL-1 signaling is suggested to be a consequence of Akt mediated activation of the mTOR pathway, which has been linked with cell cycle progression."

reach
"Akt is then released into the cytosol to activate mTOR through PDK1."

reach
"MTOR activation by Akt leads to cell proliferation and survival by modulating critical molecules such as cyclin D1."

reach
"Akt is known to activate mTOR, which in turn regulates protein synthesis and cell proliferation through the phosphorylation and activation of S6 kinase and S6RP."

sparser
"MTOR is also activated by Akt in response to mitogens."

reach
"GSK-3beta is a constitutively activated protein inhibited following Akt activation, while mTOR is activated by Akt [44, 45]."

reach
"In this pathway, AKT (protein kinase B) suppresses AMPK (AMP activated protein kinase) and, in turn, blocks the inhibition of MTOR (mechanistic target of rapamycin) by AMPK, leading to MTOR activation."

sparser
"Akt activation of the mammalian target of rapamycin (mTOR) leads to protein synthesis, allowing protein accumulation, cell growth and the preparation of cells for mitosis, all events that favor tumor growth."

reach
"Akt in turn activates mTOR through inhibition of the mTORC1 repression factor Tuberous Sclerosis Complex (TSC)."

reach
"However, the mechanism by which Akt activates mTOR is not fully understood."

sparser
"PI3K AKT mTOR activation can inhibit glycolysis ( xref )."

reach
"XREF_BIBR As a downstream effector of PI3K, Akt can activate mTOR, while mTORC2 phosphorylates Akt at Ser473."

reach
"A proposed via responsible for myocyte hypertrophy is the increased insulin sensitivity and hyperactivity of Akt, that results in activation of mammalian target of rapamycin (mTOR) and inactivation of forkhead box O transcription factor–signaling pathways ."

reach
"Whereas Akt upregulates mTOR, AMPK downregulates mTOR."

reach
"KRAS induced autophagy was mediated through upregulation of the RAS/RAF/MEK/ERK pathway and downregulation of the PI3K and AKT pathway, known to activate the autophagy inhibitor mTOR."

reach
"Normally, the activated PI3K phosphorylates protein kinase B (AKT) and stimulates the mammalian target of rapamycin (mTOR) pathways [76]."

sparser
"With heightened levels of insulin there is also increased PI3K production of phosphatidylinositol (3,4,5)-triphosphate (PIP3), activation of Akt (AKR mouse thymoma) kinase and increased nuclear SREBP-1 levels via Akt activation of the mammalian target of rapamycin (mTORC1) signaling complex ( xref ) [ xref ]."

reach
"CK2 directly phosphorylates NF-kappaB p65 and IkappaB to enhance NF-kappaB signaling, and phosphorylates AKT to activate the mTOR pathway 8."

sparser
"Melatonin prevented the injury-induced decrease in Akt activation and phosphorylation of mTOR and p70S6 kinases, and the subsequent decrease in S6 phosphorylation."

reach
"At the molecular level, liver tumors induced by AKT and c-Met display activation of AKT and mTOR and Ras and MAPK cascades as well as increased lipogenesis and glycolysis."

sparser
"In turn, phosphorylated Akt activates mTOR which phosphorylates S6."

reach
"Sensitization to INCB in myr-AKT-expressing cells could be fully restored with an allosteric AKT inhibitor, MK-2206 (XREF_FIG), but not with the dual phosphoinostitide 3- kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor BEZ-235 (XREF_SUPPLEMENTARY), suggesting that resistance in these cells does not depend on AKT mediated mTOR activation."

reach
"As a strong evidence of this concept, siRNA-mediated gene silencing of AKT inhibited the activation of mTOR and subsequently led to the suppression of migration, invasion, and proliferation [46]."

eidos
"After that , AKT promotes the mammalian target of rapamycin ( mTOR ) ( Hay and Sonenberg , 2004 ) and inhibits the forkhead box transcription factor ( FOXO ) ( Wang et al ., 2014 ) ."

reach
"IGF-1 treatment activated protein kinase B (AKT), which may inhibit autophagy via the AKT and mammalian target of rapamycin signaling pathway."

reach
"In contrast, l-tryptophan treatment did not affect AKT phosphorylation, suggesting that l-tryptophan-mediated mTOR activation is not induced by AKT activation."

reach
"Activated PI3K phosphorylates Akt, which then activates mTOR and p70S6 kinase to turn on the IGF-PI3K and Akt-mTOR-S6K axis of signaling pathway."

reach
"In the present study, we have also shown that the IAV infection activates N-Ras, which further phosphorylates Akt and activates the downstream mTOR signaling proteins."

reach
"MTOR is activated by the phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt and PKB) pathway [XREF_BIBR], (XREF_FIG)."

sparser
"Akt also phosphorylates and activates mTOR [346], which causes phosphorylation of p70S6K and PHAS-1/4E-BP1, activating protein synthesis and translation initiation, respectively [347]."

reach
"In response to IGF-1, Akt activates downstream effectors, mTOR and p70S6K to stimulate protein synthesis thereby increasing the cytoplasmic compartment in muscle fibers."

reach
"Various inhibitors of mTOR and/or PI3K and AKT can suppress the OCT4 and mTOR axis in malignant brain tumors."

reach
"PKB and Akt activates mTOR, which subsequently results in 4E-BP1 phosphorylation [32]."

reach
"It has been previously shown that BMP2 increases Akt serine/threonine kinase activity in serum deprived 2T3 cells XREF_BIBR, and Akt and PKB signaling is known to activate mTOR pathway."

reach
"This in turn produces phosphatidylinositol 4,5-bisphosphate and 3,4,5-trisphosphate to activate Akt, which activates mTOR and inhibits autophagy."

reach
"Although it is well known that mTOR was activated by the PI3K and AKT pathway, it is also activated by AKT independent regulation, such as mitogen responsive, energy sensing, hypoxia and amino acids [XREF_BIBR]."

reach
"This reduction was mediated by AKT dependent activation of mTOR complex 1, which in turn induced the differential translation of the dominant negative C/EBPbeta isoform, liver inhibitory protein (LIP)."

reach
"Subsequently, activated PI3K or Akt may positively regulate mTOR, leading to increased phosphorylation of ribosomal p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), the two best characterized downstream effector molecules of mTOR."

reach
"Among these signaling pathways is the PI3K and AKT pathway, which activates mTOR in response to growth factors such as insulin or insulin like growth factors."

reach
"MTOR is activated by AKT phosphorylation (p-mTOR)."

reach
"MTOR activity is mediated by the PI3K and Akt signaling pathway, through phosphorylation of tuberin (TSC2) and activation of Rheb, stimulating cellular growth."

reach
"For instance, in conditions of energy or nutrient surplus, growth factors, such as insulin, may trigger the PI3K and Akt pathway, which then stimulates the mTOR pathway and promotes increased cell growth and metabolism."

eidos
"In addition , AKT stimulates the mTOR , a serine / threonine kinase that is part of two distinct complexes , mTOR Complex ( TORC ) 1 , and TORC2 which directly control cell metabolism and growth in response to environmental signals [ 35 ] ."

reach
"Phosphorylated Akt activates mTOR and promotes the synthesis of proteins, which participate in T-cell division, proliferation and survival (Fig. 2)."

reach
"AKT also activates the mTOR complex 1 through phosphorylation and inhibition of TSC2, ultimately stimulating cell growth and proliferation 240."

reach
"Consistent with the incompetence of constitutive activation of Akt or inhibition of AMPK to rescue mTOR signaling, disruption of the function of TSC1 and TSC2 complex only marginally rescued curcumin mediated inhibition (XREF_FIG)."

reach
"Consistently, phosphorylation of mTOR and its downstream target proteins p70S6K and 4EBP1 were induced in S1tg mice, supporting the notion that Akt activates mTOR XREF_BIBR - XREF_BIBR."

reach
"It is concluded that Akt stimulation of mTOR and subsequent activation of the targets by which mTOR affects protein translation are required and sufficient mechanisms for Akt mediated survival of beta cells undergoing sustained AMPK activation."

reach
"Akt, Tuberin and Rheb activate mTOR when it is part of a protein complex called mTORC1 (mTOR complex 1), which is exquisitely sensitive to the drug rapamycin."

reach
"MTOR is activated by Akt, leading to phosphorylation of eIF4E binding proteins (4EBPs), which activates Eif4E."

reach
"These findings provide a mechanism of opioid-induced tolerance and hyperalgesia in which μ opioid receptor activation activates PI3K/Akt which triggers an mTOR-dependent signaling cascade that results in increased protein translation (Fig. 3) [19]."

reach
"The PI3K and Akt signaling up-regulates mTOR activity by alleviating repression of mTOR by the TSC2 complex [XREF_BIBR]."

sparser
"AKT directly phosphorylates and activates mTOR."

reach
"In skeletal muscle, Akt activates the mTOR and P70-S 6K protein synthesis pathway that induces muscle hypertrophy [XREF_BIBR, XREF_BIBR]."

reach
"In particular, Akt activates the mTOR pathway, inhibits pro-apoptotic caspase 3, and phosphorylates NF-κB, which up-regulates the anti-apoptotic proteins Bcl-2 and Bcl-xL (122,123)."

reach
"During the early stage of I/R, autophagy was excessively activated, and the treatment of bFGF stimulated phosphorylation of PI3K and Akt then further enhanced mTOR signaling to result in autophagy inhibition."

reach
"The mTOR is activated by functional inactivation of tuberin after its phosphorylation by Akt 16, 17."

reach
"Akt is upstream and positively regulates mTor while active AMPK inhibits mTor."

sparser
"Activation of mTOR by Akt stimulates protein synthesis through the actions of the ribosomal protein S6 kinase (S6K) and the translational initiation factor eIF-4E-binding protein 1 (4EBP1) ( xref ; xref )."

reach
"However, upon Akt mediated activation of mTOR, these latter mRNAs are highly and disproportionately translated."

reach
"We further wanted to investigate whether IAV modulates the mTOR pathway, which is activated by the crucial signaling protein Akt, which in turn is activated by Ras proteins."

reach
"In addition, pharmacologic inhibition of PI3K and AKT down-regulates the activation of the mTOR signaling pathway."

sparser
"Then, Akt activates mTOR via the inhibition of tuberous sclerosis 1/2 (TSC1/2)."

reach
"AKT positively regulates mTOR (activator of PGC-1alpha) by direct inhibition of the inhibitory complex TSC1/2 and by inhibition of the mTOR inhibitors AMPK (activator of PGC-1alpha) and GSK3beta (regulator of PGC-1alpha turnover) [XREF_BIBR, XREF_BIBR]."

reach
"Next, we analyzed the phosphorylation levels of AKT (ser473) and S6 (a downstream target of mTOR) by western blot."

reach
"[XREF_BIBR] In the present report, inhibition of Akt reduced the basal activity of mTOR, suggesting mTOR may be an important downstream mediator of Akt."

sparser
"Phosphorylated AKT activates mTOR complex 1 (mTORC1), which later releases eIF4E by phosphorylation of eIF4E-binding protein (4EBP1)."

sparser
"Akt activates the mTOR complex to promote protein synthesis and cell growth."

sparser
"Akt activates the mammalian target of rapamycin (mTOR) by either direct phosphorylation or by inactivation of tuberous sclerosis protein (TSC, harmatin) ( xref ; xref )."

reach
"PI3K signals to Akt, which activates the mTor complex, leading to migration of cancer cells."

sparser
"PIP3 subsequently binds to phosphoinositide-dependent kinase 1 (PDK1), thus phosphorylating and activating the serine/threonine kinase AKT. xref , xref PTEN (phosphatase and tensin homolog), a tumor suppressor, is a phosphatase that dephosphorylates PIP3 into inactive PIP2, thereby dampening AKT and PDK1. xref , xref Activated AKT can phosphorylate and activate mTOR or indirectly promote mTOR activity by phosphorylation and inactivation of tuberous sclerosis complex 1/2, a mTOR inhibitor."

sparser
"PI3K activates a number of downstream targets including the serine/threonine kinase Akt that activates mTOR."

sparser
"Phosphorylated Akt activates mTOR complex 1 (mTORC1), causing increased mRNA translation, protein synthesis and cellular proliferation."

sparser
"AKT activates mTOR through TSC1/2 leading to protein synthesis and cell growth [ xref ]."

reach
"Akt activates mTOR via phosphorylation and inactivation of tuberous sclerosis complex (TSC)-2."

sparser
"Following activation, Akt directly activates mammalian target of rapamycin complex 1 (mTORC1) by phosphorylating mTORC1 at Ser2448 xref ."

reach
"Conversely, mTOR complex 1/S6 kinase 1 (mTORC1 and S6K1) activation by IGF-1R and PI3K-Akt is required for GLP-1-induced beta-cell proliferation."

reach
"Since the oncogenic mutations in PIK3CA induce downstream signaling through the phosphorylation of AKT and subsequent activation of mTOR complex 1 (mTORC1), inhibition of PI3K, AKT, and/or mTORC1 may be an effective therapeutic strategy to treat the tumors with an oncogenic PIK3CA mutation."

reach
"We also provide evidence that suppression of AMPK activates mTOR and survival signaling mediated by the Akt pathway."

reach
"Our data demonstrate that the inhibition of inappropriately high Akt decreases mTOR kinase activity in IPF fibroblasts (XREF_FIG)."

reach
"Then, BDNF interacts with tropomyosin receptor kinase B (TrkB) receptors and Akt and ERK signalling, which increase downstream mTOR activation [XREF_BIBR, XREF_BIBR]."

sparser
"With heightened levels of insulin there is also increased PI3K production of phosphatidylinositol (3,4,5)-triphosphate (PIP3), activation of Akt (AKR mouse thymoma) kinase and increased nuclear SREBP-1 levels via Akt activation of the mammalian target of rapamycin (mTORC1) signaling complex (Figure 3) [88]."

sparser
"Akt, an important downstream effector of PI3K, activates mTOR and p70S6 kinase which in turn regulates the 40S ribosomal protein S6 to control protein synthesis and cell proliferation."

reach
"Previous studies showed that mTOR was critical for autophagy induction, and the upstream PI3K-Akt signaling could activate mTOR thus suppressed autophagy, while repressed mTOR in the absence of growth factors could active autophagy."

reach
"Interestingly, AKT and ERK can activate the mTOR and S6K1 pathway by inhibiting the TSC1/2 complex."

reach
"Akt signaling promotes proliferation indirectly by activating the mTOR pathway that controls translation of peptides necessary for cell growth, and directly by phosphorylating multiple cyclin dependent kinase inhibitors."

reach
"IGF-1 induces the phosphorylation of Akt which then activates mTOR and its downstream targets p70S6k and 4E-BP to initiate protein translation and synthesis XREF_BIBR, XREF_BIBR."

reach
"To obtain further support for this assumption, we studied the responses of the well established downstream targets of AKT, glycogen synthase kinase 3beta (GSK3beta) and S6 ribosomal protein (S6), downstream of the growth promoting mammalian target of rapamycin (mTOR) complex."

sparser
"In addition to those actions, AKT indirectly activates mTOR through inhibition of TSC2, while mTORC2 also responds to UV by forming into a complex with DNA-PKcs to phosphorylate AKT at Ser-473 [ xref ]."

eidos
"Akt is then able to activate mammalian target of rapamycin ( mTOR ) , which is a regulator of protein synthesis and cell survival ( Memmott and Dennis , 2009 ) ."

sparser
"Translation of MYC mRNA is partly regulated by mammalian target of rapamycin (mTOR), which is activated by AKT after its phosphorylation by phosphoinositide 3-kinase (PI3K) [ xref ]."

sparser
"Akt activates mTOR, promoting anabolic metabolism and fatty acid synthesis, whereas AMPK represses mTOR, leading to catabolic energy production and fatty acid oxidation."

reach
"The PI3K and Akt signalling up-regulates mTOR activity by alleviating repression of mTOR by the TSC2 complex [XREF_BIBR]."

sparser
"Through TSC and RHEB, AKT activates the mammalian target of rapamycin (mTOR)."

reach
"RAF1 is a member of the PI3K and AKT signaling cascade, which is known to activate the mTOR pathway XREF_BIBR."

reach
"In addition to those actions, AKT indirectly activates mTOR through inhibition of TSC2, while mTORC2 also responds to UV by forming into a complex with DNA-PKcs to phosphorylate AKT at Ser 473 [XREF_BIBR]."

eidos
"AKT activates mTOR by inhibiting the formation of TSC1 / TSC2 composite and PRAS40 , an important negative regulatory factor in this pathway 78 ."

reach
"While AKT stimulates mTOR pathway through PRAS40 and further activates p70S6, S6, and 4E-BP1, PDK1 may play a role in activating MEK mediated MAPK pathway, where PDK1 interacts with and activates MEK and also p90RSK to activate the MAPK signaling pathway."

reach
"The mammalian target of rapamycin (mTOR) pathway may be activated by PI3K and Akt signaling, as well as by AA [XREF_BIBR], to alter lipid metabolism and stimulate anabolic growth in breast cancer cells [XREF_BIBR]."

reach
"Earlier studies showed that mTOR activated by Akt leads to the activation of the pathways that promote protein synthesis and the inactivation of glycogen synthase [XREF_BIBR, XREF_BIBR]."

sparser
"Activated Akt activates mTOR followed by phosphorylation of ribosomal protein S6 kinase (S6K)( xref )."

trips
"Here we establish an additional pathway by which Akt inhibits TSC2 and activates mTOR."

reach
"AKT promotes activation of mTOR through AKT mediated cellular energy and inhibition of AMPK, which is an activator of TSC2 - a negative regulator of mTOR."

sparser
"MTOR is activated by Akt, leading to phosphorylation of eIF4E binding proteins (4EBPs), which activates Eif4E."

reach
"Co-expressed in fetal neural stem cells, ZIKV non structural proteins NS4A and NS4B decreased AKT phosphorylation and subsequently inhibited mTOR activation, which induced autophagy 95."

reach
"In detail, PI3K activation leads to Akt phosphorylation, which consequently activates mTOR."

reach
"These data indicated that pemetrexed and simvastatin cotreatment induces AMPK- and AKT mediated mTOR dependent autophagy in malignant mesothelioma and NSCLC cells."

eidos
"AKT in turn is an activator of mTOR ( Hahn-Windgassen et al ., 2005 ) ."

reach
"Thus, the overexpression of AKT activates mTOR signaling in goat cells."

reach
"Note: AKT, protein kinase B; COX-1, cyclooxygenase-1; cPLA2, cytoplasmic phospholipase A2; EIF2α, eukaryotic initiation factor 2 alpha; ER, endoplasmic reticulum; HK-2 cells, human kidney 2 cells; MAPK, mitogen-activated protein kinase; mitoROS, mitochondrial reactive oxygen species; mTOR, mitogen-activated protein kinase; PS-MPs, polystyrene microplastics; ROS, reactive oxygen species."

reach
"Via biochemical and genetic approaches, the kinases IKKi and GSK3alpha were identified as the critical intermediate signaling components for IL-1-induced AKT activation, which in turn activated mTOR."

reach
"The upstream activator of mTOR, Akt, also exhibited increased phosphorylation at threonine 308 (p-Akt-T308) and serine 473 (p-Akt-S473) (Figure 6C-D)."

reach
"Akt activates mTOR through (i) phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2), which inactivates the mTOR activating GTP binding protein Rheb, and/or (ii) phosphorylation of PRAS40 a member of mTORC1, one of the two functional complexes of mTOR, which includes mLST8 and Gbl and the scaffold protein Raptor."

reach
"The regulation mTOR activity by growth factors is mediated by the PI3K and Akt signaling pathway [XREF_BIBR], activated by not just IGF-I, but also insulin and PDGF."

reach
"Increased glycolysis and ATP production is the predominant pathway by which AKT activates mTOR and tumorigenesis [XREF_BIBR]."

eidos
"Future work still needs to detail the particular mechanisms by which Akt elicits mTOR activity ."

sparser
"AKT activates mTOR to become phosphorylated mTOR (p-mTOR) through TSC1/2."

reach
"Akt also inhibits mammalian target of rapamycin in gliomas, which regulates various cellular reactions, such as cytoskeletal architecture, transcription, and autophagy, to enhance cell viability XREF_BIBR."

reach
"Moreover, the phosphorylation of mTOR and its direct substrate p70 S6 kinase was augmented by HSV-1 infection, while the mTOR stimulator Akt and inhibitor AMPK activated protein kinase (AMPK) were accordingly activated and suppressed, respectively."

reach
"Moreover, Akt also indirectly activates mTOR which is involved in cell growth and metabolism via phosphorylation and inhibition of tuberous sclerosis complex 1/2 (TSC 1/2) [113,114]."

sparser
"PI3K activates AKT which activates mammalian target of rapamycin (mTOR)."

reach
"The activation of AKT through phosphorylation is known to activate mTOR (mammalian target of rapamycin), which regulates a variety of functions associated with tumor pathogenesis XREF_BIBR, XREF_BIBR."

reach
"AKT indirectly activates mTOR, a complicated checkpoint of cellular growth influenced by growth factor signaling, adenosine monophosphate levels, and nutrient and O 2 availability [XREF_BIBR]."

sparser
"AKT indirectly activates mTOR, a complicated checkpoint of cellular growth influenced by growth factor signaling, adenosine monophosphate levels, and nutrient and O2 availability [ xref ]."

reach
"AKT activates the mTOR containing complex 1 (TORC1) which, via S6K and 4E-BP1, regulates mRNA translation and protein synthesis."

reach
"PtdIns (3,4,5) P 3 in turn recruits both phosphatidylinositol dependent kinase 1 (PDK1) and AKT and PKB to the membrane where PDK1 phosphorylates and activates AKT and PKB and indirectly activates the mTOR."

reach
"The PI3K and Akt pathway results in activation of mTOR."

reach
"Akt is a direct activator of mTOR, and both Akt phosphorylation (T308 and S473) and phosphorylation of Akt targets (GSK3beta, PRAS40) were elevated in ErbB2 positive tumors lacking LKB1."

reach
"Growth factor and oncogene signaling activate PI-3 kinase and its downstream effector AKT, a protein kinase that activates mTOR via inhibition of TSC-1 protein."

reach
"Here we establish an additional pathway by which Akt inhibits TSC2 and activates mTOR."

reach
"In turn, activated Akt induces mTOR activity, which leads to the activation of multiple downstream targets, including 4E-BP1 and S6K1 (Powell and Delgoffe, 2010)."

reach
"In one report [12 *], an inducible form of PKB was shown to increase mTOR activity towards 4E-BP1 ~ 1.5 fold, although no direct phosphorylation of mTOR by PKB was reported."

sparser
"Activated Akt activates both the rapamycin sensitive mTOR complex 1 (mTORC1) and the rapamycin insensitive mTOR complex 2 (mTORC2)."

reach
"XREF_BIBR mTOR activation by Akt has been shown through both the direct inhibition of tuberous sclerosis 2 (TSC2), a negative regulator of mTOR, XREF_BIBR and by inhibition of AMPK mediated phosphorylation of TSC2."

sparser
"AKT-dependent activation of mTOR involves the phosphorylation of tuberous sclerosis complex 2 (TSC2) and proline rich AKT substrate of 40 kDa (PRAS40) thereby relieving their inhibitory function on mTOR kinase activity."

reach
"We further provide evidence that GUTK inhibits Akt phosphorylation, thereby inhibiting the mTOR pathway in cancer cells during nutrient starvation."

reach
"Taken together, our results support the role of RARalpha in activating the signaling cascade from PI3K to Akt and subsequent activation of the mTOR pathway, which is key to increase T cell metabolism to exit metabolic quiescence."

reach
"Since activated Akt and PDK1 may positively regulate mTOR and S6K1, respectively, XREF_BIBR, we next investigated whether H 2 O 2 induction of ROS inhibits mTOR mediated phosphorylation of mTOR and S6K1 by suppressing the activity of Akt and PDK1, respectively."

sparser
"Akt takes a part in the regulation of various signaling downstream pathways, including cell proliferation, growth, survival, angiogenesis, and chemoresistance. xref As a downstream effector of PI3K, Akt can activate mTOR, while mTORC2 phosphorylates Akt at Ser473 and stimulates Akt phosphorylation at Thr308 by 3-phosphoinositide-dependent protein kinase 1, leading to full Akt activation. xref mTOR plays a key role in cell growth, autophagic cell death, and homeostasis. xref mTOR is phosphorylated at Ser2448 via the PI3K/Akt signaling pathway and autophosphorylated at Ser2481. xref mTOR inhibition promotes dissociation of mTOR from the complex of Atg13 with Unc-51 like autophagy activating kinase 1 (ULK1) and ULK2."

reach
"In the Akt and mTOR pathway, protein mTOR can be activated by Akt, which can inhibit cellular apoptosis and promote cell proliferation."

sparser
"Akt activates mTOR by phosphorylation [ xref ], and both Akt and mTOR phosphorylation are increased during muscle hypertrophy [ xref ]."

reach
"PKB and Akt activity has been linked to increased mTOR activation through several mechanisms, including direct phosphorylation of mTOR by PKB and Akt [XREF_BIBR, XREF_BIBR], PKB and Akt mediated phosphorylation of TSC2, and inhibition of AMP kinase, which prevents the phosphorylation and inhibition of TSC2 [XREF_BIBR]."

sparser
"Accordingly, co-targeting mTOR and PI3K/Akt signaling prevents mTOR inhibition-initiated Akt activation and enhances antitumor effects both in cell cultures and in animal xenograft models, suggesting an effective cancer therapeutic strategy."

reach
"The mammalian class I PI3K and its product PI (3,4,5) P3 block autophagy by activating Akt and PKB, which activates mTOR (mammalian target of rapamycin) kinase, the principal negative regulator of aut[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Studies have found that UA can induce the phosphorylation of AKT in monocytes and activate mTOR, thus inhibiting autophagy."

reach
"Phosphorylation of Akt by PIP3 activates the mechanistic target of rapamycin (mTOR) which initiates signaling that stimulates cell growth and protein synthesis."

reach
"In addition, the phosphorylation of AKT activated AKT/mTOR and suppressed autophagy [57]."

reach
"In addition, Galpha q can activate AKT kinase, which modulates mTOR and NF-kB signaling pathways."

reach
"Importantly, the mentioned anti-proliferative and pro apoptotic effects of adiponectin were seen in mostly ERalpha negative BC, while divergent effects of adiponectin were reported in ERalpha positive BC such as : (i) activation of both MAPK and Akt stimulating mTOR and p70S6K cascade, (ii) activation of ERalpha followed by recruitment of LKB1 as a receptor coactivator overall compromising AMPK and in consequence switching cancer cell energy balance vs. lipogenic aggressive phenotype, and (iii) upregulation of cyclin D1 promoting tumor growth [XREF_BIBR]."
| PMC

reach
"MTOR is activated by PI3 kinase and AKT activity and is inhibited by AMP activated protein kinase (AMPK), which is a sensor of cellular energy resources."

reach
"The Akt and mTOR pathway was activated in C 2 C 12 myoblasts treated with creatine, as Akt, mTOR, and p70S6 kinase activity were elevated [XREF_BIBR]."

sparser
"Studies using pressure overloaded mice and guinea pigs reported that P70 S6 ribosomal kinase (S6K) phosphorylation is clearly correlated with cardiac hypertrophy xref , xref , and that cardiac-specific Akt overexpression increases activation of mTOR and results in cardiac hypertrophy xref , xref , xref ."

reach
"Phosphorylation of Akt promotes activation of mTOR, and mTOR is crucial for mitochondrial metabolism and phosphorylation of S6, a surrogate of mTORC1 activity XREF_BIBR, XREF_BIBR."

sparser
"A number of feedback and feedforward regulations exist along the PI3K pathway, including negative feedback by S6K, positive feedback by mTORC2, and feedforward activation of mTOR by AKT ( xref ; xref ; xref ; xref ; xref ) ( xref )."

reach
"Activation of PI3K and AKT also activates mTOR and S6K sequentially, which meditates the feedback regulation on Ser phosphorylated IRS-1 [26]."

reach
"Akt phosphorylation activates downstream mTOR kinase."

sparser
"Intrathecal administration of mTOR inhibitors was shown to significantly block the development of inflammatory and neuropathic pain. xref , xref , xref , xref Given that mTOR is important for control of protein translation and that Akt can activate mTOR in central neurons, xref , xref it is possible that mTOR participates in Akt-dependent induction of Nav1.7 and Nav1.8 expression in DRG neurons after inflammation."

reach
"The benzimidazole anthelmintics usually decreased signaling proteins related to cell proliferation and survival, such as phosphorylated (p) HER2/3, PI3K and protein kinase B (AKT), rapidly accelerated fibrosarcoma (a family of three serine/threonine specific protein kinases) (RAF)/MEK/ERK, mTOR, and Ki-67."

sparser
"AKT in turn promotes cellular survival and activates mammalian target of rapamycin (mTOR) to increase ribosomal biogenesis and messenger RNA (mRNA) translation."

reach
"Akt and PKB signaling activates the mTOR pathway."

reach
"Activation of mTOR signaling by Akt and PKB involves the phosphorylation and inactivation of TSC2 [XREF_BIBR]."

reach
"We propose that the activation of mTOR by Akt mediated cellular energy and inhibition of AMPK is the predominant pathway by which Akt activates mTOR in vivo."

reach
"In addition, Akt activates mTOR complex 1, its effector protein S6, and translation regulator 4E-BP1 in Hp -infected cells in a PI3K- and the Src tyrosine kinases dependent manner."

reach
"Intriguingly, mechanical signaling through P13K and AKT induces mTOR."

reach
"The PI3K-Akt axis works downstream of the TCR and CD28 in T cells and ultimately activates mTOR complexes (mTORC1 and mTORC2)."

reach
"XREF_BIBR mTOR, a serine/threonine kinase downstream from AKT, is activated not only by AKT but also by RAS pathways."

reach
"PKB and Akt activity has been linked to increased mTOR activation through several mechanisms, including direct phosphorylation of mTOR by PKB and Akt [XREF_BIBR, XREF_BIBR], PKB and Akt mediated phosphorylation of TSC2, and inhibition of AMP kinase, which prevents the phosphorylation and inhibition of TSC2 [XREF_BIBR]."

reach
"Mammalian target of rapamycin (mTOR), a Ser/Thr protein kinase of rapamycin-targeted protein, could be activated by AKT and MAPK signaling to inhibit autophagy and down-regulated by AMPK and p53 signaling to promote autophagy (Agarwal et al., 2015)."

reach
"Moreover, the kinases GSK3beta and mTOR, modulated by PI-3K and Akt, can inhibit NFAT activity, suggesting a cross-talk between the calcium and growth factor signaling pathways."

"It was shown recently that akt activates mtor through direct phosphorylation of tsc2 the serine/threonine kinase akt is an upstream positive regulator of the mammalian target of rapamycin (mtor). However, the mechanism by which akt activates mtor is not fully understood. The known pathway by which akt activates mtor is via direct phosphorylation and tuberous sclerosis complex 2 (tsc2), which is a negative regulator of mtor."

reach
"The delicate process of starvation induced autophagy XREF_BIBR is inversely regulated by mTOR which is activated by PI3K-Akt induced by insulin or other growth factor XREF_BIBR, XREF_BIBR."

reach
"Of note, both ERK and Akt contribute to mTOR hyperactivation, thus identifying mTOR as a potential common target of drug intervention, as supported by the beneficial effects of RAD001."

sparser
"Akt directly phosphorylates and activates mTOR, as well as inhibits the mTOR inhibitor proteins PRAS40 and tuberin."

sparser
"Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity."

sparser
"PI3K signals to Akt, which activates the mTor complex, leading to migration of cancer cells."

reach
"Taken together, these results indicate that there could be an unknown pathway through which AKT activates S6 and eIF4E independent of mTOR function or that mTOR may be influenced by additional signaling pathways in response to genetic changes or metabolic changes independently of AKT in NSCLC."

reach
"Our results show that inhibition of AKT potentiates the efficacy of mTOR inhibition both in vitro and in a xenograft mouse model in vivo."

sparser
"MTOR is a key regulator and can be activated by phosphorylated-AKT."

reach
"Moreover, T-cell metabolism is also mediated by AKT signaling which increases utilization of glucose and amino acids and promotes the mTOR pathway and glycolysis, thus supporting effector T-cell differentiation, growth, and function [XREF_BIBR]."

reach
"AKT also activates the mechanistic target of rapamycin (mTOR) and induces cellular senescence (Johnson, Rabinovitch, & Kaeberlein, 2013)."

sparser
"In normal cells, PI3K activation is tightly controlled by dephosphorylation of PIP3 by the phosphatase PTEN, a potent tumor suppressor. xref Together, mutations in PI3K signaling constitute one of the most common mutations in human tumors. xref Enhanced PI3K/Akt signaling selectively gives tumors an advantage through several pathways, including (1) increased surface expression of nutrient transporters resulting in increased uptake of glucose, (2) Akt-dependent stimulation of hexokinase and phosphofructokinase to drive glycolysis, (3) enhanced transcription of genes involved in glycolysis, and (4) enhanced protein translation through Akt-dependent mTOR activation. xref "

reach
"This is due to the fact that mTOR, which is activated by the PI3K and Akt pathway, promotes cell growth and proliferation, cytokine production and signalling, all of which are essential for an efficient immune response [XREF_BIBR]."

reach
"In this study, we have shown that activation of beta-catenin and/or AKT increases mTOR activity and that inhibition of that activity with rapamycin suppresses the tumor burden by controlling cell proliferation and death."

eidos
"IGF1 activates AKT , AKT activates mTOR and inhibits FOXO , FOXO inhibits mTOR and promotes atrophy , mTOR promotes hypertrophy ."

reach
"Upon IGF-1 stimulation, PI3K and AKT activates mTOR [XREF_BIBR], then Raptor is combined with mTOR to form mTORC1, which alters the activity of EIF4E-BP1 by phosphorylation [XREF_BIBR]."

reach
"Since mTOR activation can be stimulated by the upstream PI3K-Akt pathway XREF_BIBR, we next investigated the effect of inhibiting Akt activation."

reach
"Akt (aka protein kinase B) is activated by insulin and IGF-1 and has two known major downstream branches relevant to muscle protein synthesis : the mTOR pathway, which is activated by Akt, and the GSK3beta pathway, which is inhibited by Akt."

reach
"One possibility is that mTOR is directly regulated by Akt, an idea which is supported by the evidence that mTOR is a direct substrate of Akt [24]."

reach
"Based on the prediction that the activations of Akt and ERK induced by echinacoside will activate their downstream target mTOR signaling [6] , echinacoside may exhibit rapid antidepressant effects."

sparser
"Upon recruitment to the membrane, AKT is phosphorylated and in turn activates mammalian target of rapamycin (mTOR), a serine threonine kinase and other proteins involved in cell survival and proliferation (Fig.  xref )."

reach
"In conclusion, Akt mediated mTOR inactivation originating by SAHA treatment promotes ULK1 activation and thereby induces autophagy."

sparser
"Akt, in turn, can activate mTOR by direct phosphorylation and indirectly through inhibition of the tumor-suppressor complex, composed of TSC1 and TSC2 (for review see xref )."

sparser
"PIP3 synthesized by PI3K is able to activate the AkT protein which in turn activates the mTOR transcription factor."

reach
"Similarly, mTOR pathway activation by Akt allows the cell to regulate metabolism and divide and proliferate."

reach
"Notably, overexpression of constitutively active AKT (CA-AKT) which rescues p-AKT and downstream mTOR pathways, significantly protected cells suggesting the critical role of p-AKT inhibition in apoptosis induced by the combination of EGCG and resveratrol."
| PMC

eidos
"A second pathway regulating eIF4F is PI3 kinase , which activates Akt , which activates mTOR ."

sparser
"Subsequently, Akt activates mammalian target of rapamycin (mTOR) and regulates down stream effector p70 ribosomal protein S6 kinase (p70S6K) and 4E-BP1, both of which control protein synthesis (Rommel et al., xref )."

reach
"Akt and PKB phosphorylation induces mTOR activation and apoptosis inhibition."

trips
"The known pathway by which Akt activates mTOR is via direct phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2), which is a negative regulator of mTOR."

reach
"Patient selection based on molecular events known to be associated with mTOR activation such as the overexpression of PI3K and Akt and the growth factor receptors human epidermal growth factor receptor 2 (HER2) and insulin like growth factor receptor (IGFR) as well as mutations in PI3K and mutations and amplifications of Akt or downregulation of PTEN may represent an appropriate way to identify populations that are more likely to show significant benefit from mTOR inhibitors."

sparser
"Downstream in the insulin signaling pathway, Akt activates mammalian target of rapamycin complex 1 (mTORC1) by directly phosphorylating and inhibiting tuberin in tuberous sclerosis complex 2 (TSC2) ( xref – xref )."

reach
"This releases ULK1/2 to activate FIP200, a protein critical for autophagosome formation and autophagy initiation; as an upstream effector of mTOR, Akt can activate mTOR via direct phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2), which is a negative regulator of mTOR."

sparser
"It was reported that Akt activates mTOR by phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2)."

reach
"MTORC1 activation requires binary inputs from growth factor induced Akt mediated signaling that activates mTOR, and repletion of intracellular amino acids, which enables translocation of mTORC1 to lysosomal membranes where mTOR activation occurs 18."

sparser
"AKT in turn activates the mechanistic target of rapamycin (mTOR), which is a key sensor that integrates nutrient- and growth factor-derived cues to coordinate anabolic metabolism ( xref )."

reach
"As the most important downstream signal molecule of PI3K and Akt, mTOR is activated by Akt phosphorylation, and the expression of mTOR is abnormally increased in tumor progression."

reach
"PI3K/AKT pathway is believed to stimulate the activation of the mTOR pathway, which promotes the synthesis of growth factors like VEGF [24, 25]."

reach
"The IGF-I system regulates the mTOR axis through the phosphorylation and inhibition of the TSC1/2 complex by Akt, which in turn activates Rheb and mTOR."

reach
"As activation of both p44 and p42 MAPK and Akt inhibits not only apoptosis, but also autophagy via activation of the mammalian target of rapamycin, 34 their activation should be involved in determining the mode of cell death, thus leading to necrosis, but not to apoptosis, after ULMW-HA stimulation."

sparser
"Akt can activate mTor directly ( xref ) and indirectly through activation of Tsc and inhibition of Rheb ( xref )."

reach
"24 Therefore, we examined whether BAFF can activate the AKT and mTOR pathway (activation of AKT phosphorylation, and up-regulation of mTOR downstream effectors, such as p70S6K, p-4E-BP1, and eIF4E) in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The phosphorylation of AKT activates mTOR (mammalian target of rapamycin), which leads to cell division [XREF_BIBR]."

reach
"Both AKT and ERK can activate mTOR by phosphorylating mTORC1 regulators, such as tuberous sclerosis 2 protein (TSC2)."

reach
"MTORC2 can phosphorylate AKT at the Ser473 residue and thus induce the AKT signaling cascade and still increase mTOR activation; through this feedback loop, cancer cells can develop resistance to mTOR targeting therapies."

reach
"MTOR can be activated by several stimuli such as growth factors, nutrients through receptor tyrosine kinase (RTK), phosphatidyl inositol 3 kinase (PI3K), and Akt and PKB signaling cascade [13]."

reach
"Next, we knocked down the gene expression of Akt downstream targets of mTOR and 70S6K through gene specific morpholino injection."

reach
"Akt activates mTOR by phosphorylation at Ser2448."

sparser
"Phosphorylated Akt can activate mTOR in central neurons xref , and peripheral inflammation initiates spinal activation of the PI3K/Akt/mTOR signaling pathway xref ."

reach
"This further suggests that BCAAs and glutamic acid can be considered candidate biomarkers for liver cancer since they are known to activate Akt driven mTOR pathway as described above."

reach
"In D. gliroides, an induction of mTOR by Akt signaling could be complemented by the predicted targeting of 32 mTOR pathway genes through the action of 23 miRNAs that were suppressed in liver (XREF_TABLE and XREF_FIG)."

reach
"Mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) activate mTOR via the interaction of tuberous sclerosis complex (TSC) 1/2, Rheb, and the mammalian target of rapamycin complex 1/2 (mTORC1/2)."

reach
"The PI3K and Akt pathway activates mTOR and forkhead box protein O1 (FOXO1) and the MAPK and ERK cascade."

sparser
"Therefore, as expected, AKT-dependent mTOR activation prevents autophagy [for a review on mTOR refer to [ xref ]]."

reach
"22 In gastric cancer cells, Akt is an activator of mTOR."

sparser
"Upon activation by receptor tyrosine kinases or G-protein coupled receptors, AKT activates mTOR, which in turn stimulates protein translation through inhibitory phosphorylation of eukaryotic translational initiation factor eIF4E-binding protein 1 (4E-BP1) that inhibits eIF4E, and activating phosphorylation of p70S6 kinase (S6K) that phosphorylates ribosomal S6 protein."

sparser
"AKT separately phosphorylates and activates mTOR, which promotes cell cycle progression and growth and provides positive feedback via phosphorylation of AKT."

reach
"PI3K-Akt signaling activates mTOR mediated epileptogenesis in organotypic hippocampal culture model of posttraumatic epilepsy."

reach
"For example, Akt increases cellular proliferation via tuberin inactivation and the subsequent activation of mTOR."

reach
"AKT can also activate mTOR, a second key regulator of cell growth, by inhibiting TSC2 or blocking PRAS40 35."

sparser
"One of the kinases that mediate mTOR activation by Akt is the AMP-activated protein kinase (AMPK)."

reach
"Akt blocks mammalian target of rapamycin complex 1 (mTORC1) inhibitor tuberous sclerosis proteins 1 and 2 (TSC1/2)."

eidos
"PI 3-K and Akt that enhance mTOR activity also are critical pathways that provide cellular protection through EPO ."

reach
"PI3K is activated by increased expression of the NKA α-subunit and phosphorylates Akt, which activates mTOR."
| PMC

reach
"Crizotinib inhibited aberrant AKT and ERK phosphorylation induced by everolimus, and more effectively suppressed the activity of mTOR than everolimus monotherapy, resulting in increased G0/G1 cell-cycle arrest, DNA damage, and apoptosis."

reach
"A critical downstream signaling branch is AKT mediated activation of mTOR complex 1 (mTORC1), which leads to protein translation and lipid or nucleotide synthesis."

reach
"Thus, inhibition of AKT fails to block IL-7-induced mTOR activation."

sparser
"Akt activates mTOR, which is a known negative regulator of autophagy xref , xref ."

reach
"Furthermore, Itraconazole also inhibits the phosphorylation of p70S6K, 4E-BP1, and AKT and hence suppresses the PI3K/mTOR signaling pathway [214] ."

reach
"It is now clear that AKT upregulates mTOR by phosphorylating and inhibiting the activity of the tuberous sclerosis complex-2 (TSC2) [23-25], thereby reducing GAP (GTPase activating protein) activity o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"AKT activates the mechanistic target of rapamycin (mTOR) which in turn phosphorylates the S6 ribosomal kinase."

eidos
"MTOR is activated by AKT and regulates cell survival , migration , and proliferation22 ."

sparser
"AKT phosphorylates and activates the protein kinase mammalian target of rapamycin (mTOR), which is a convergence node of many signalling pathways, particularly by regulating protein translation and cell growth ( xref )."

sparser
"However, in response to high level of ATP, Akt activates mTOR through inhibition of AMPK-mediated phosphorylation of TSC2 on T1227 and S1345 [ xref ]."

reach
"Further studies showed that UASR1 activated AKT and AKT mediated mTOR signaling pathway to stimulate cell proliferation and growth."

reach
"However, upon Akt mediated activation of mTOR, these latter mRNAs are highly and disproportionately translated."

reach
"Then, in non small cell lung cancer cells, it was shown that DHA induced apoptosis and autophagy were associated to mTOR suppression induced by both AMPK activation and PI3K and Akt inhibition; these data were confirmed in Fat-1 transgenic mice implanted with Lewis lung cancer cells [XREF_BIBR]."

sparser
"The PI3K/AKT/mTOR pathway, the most crucial upstream signalling pathway of autophagy, is well established as a regulator of a wide range of cellular processes that mediate cell survival and death, and this pathway is inhibited by malnutrition, hypoxia, external pressure or other stress conditions to suppress cell proliferation and enhance autophagy, eventually leading to cell death. xref , xref Akt is a member of the serine/threonine protein kinase family and is activated in a PI3K‐dependent manner in response to various stimuli. xref Phosphorylated class I PI3K and Akt activate mTOR. xref mTOR is a downstream target of the PI3K/AKT pathway. xref mTOR kinase is part of two mTOR complexes, mTORC1 and mTORC2, each of which has a different protein component. xref mTORC1 is a major negative regulator of autophagy. xref Inhibition of mTORC1 causes TFEB dephosphorylation and nuclear translocation, which subsequently increases lysosome biogenesis, and affects autophagic flux. xref , xref , xref Suppression of PI3K and Akt signalling inhibits mTOR phosphorylation at Ser2448, thereby inducing autophagy and increasing the levels of autophagy‐related proteins. xref Activation of this pathway promotes cell growth, differentiation and survival while down‐regulating apoptotic signals. xref , xref The ULK1 protein kinase is a key regulator of autophagy initiation and progression. xref In vitro, the mechanical induction of autophagy is TOR independent. xref However, there may be differences between in vivo and in vitro studies."

sparser
"Since mTOR is activated by Akt, although it is not clear if this is a direct or indirect activation [reviewed in [ xref ]], we decided to monitor if Akt was activated by IR by studying its phosphorylation state, which was reported to be an early response to IR [ xref , xref ]."

reach
"HIF-1alpha is not only stimulated through PI3K and AKT activation of mTOR via loss of the TSC1/2 complex, but also via mutational changes leading to loss of TCS2 function."

sparser
"The mTOR activity is negatively regulated by the tuberous sclerosis complex (TSC) composed of TSC1 and TSC2; AKT activates mTOR by inhibiting TSC ( xref )."

reach
"Akt and PKB phosphorylation induces mTOR activation and apoptosis inhibition."

sparser
"Activated Akt phosphorylates and activates mTOR, which leads to the inhibition of autophagy through the phosphorylation of multiple autophagy-related proteins and blocks the elimination of aggregates."

reach
"Then, Akt regulates many substrates activation and promotes cell growth and proliferation by activating the mTOR and p70S6K signaling pathway [XREF_BIBR - XREF_BIBR]."

reach
"AKT activation is known to trigger many downstream components of the mTOR pathway including p70S6K and 4E-BP1."

reach
"In addition, myostatin mediated Smad signaling activation inhibits protein synthesis in muscle tissues by suppressing the Akt mediated mTOR signaling pathway."

reach
"AKT activation can also enhance protein synthesis by activating mTOR signaling."

sparser
"In brief, these authors showed that loss of PTEN results in activated Akt, which in turn activates mTOR."

reach
"In fact, blockade of PI3K and Akt can decrease the activation of mTOR, an important inhibitor of autophagy induction [XREF_BIBR]."

sparser
"The PI3K enzyme itself antagonizes the tumor-suppressor PTEN, and the loss of PTEN increases glycolysis by activation of AKT and HIF-1. xref AKT stimulates glycolysis by increasing the expression and membrane translocation of glucose transporters, and also by phosphorylation of glycolytic enzymes, such as hexokinase (HK) and phosphofructokinase (PFK). xref , xref Moreover, AKT activates mammalian target of rapamycin (mTOR), which indirectly affects other metabolic pathways by activating HIF-1, even under normoxic conditions. xref Oncogene mutation of Ras activates mTOR via the PI3K-Akt-mTOR signaling pathway, and mTOR promotes glycolysis through inducing HIFs. xref , xref , xref , xref , xref The HIFs are transcription factors that regulate gene expression in response to the cellular environment, specifically in the event of decreased oxygen or hypoxia."

reach
"Because mTOR is activated by Akt, the status of mTOR in ethanol treated hepatocytes relies on the extent of impaired Akt and AMPK by ethanol."

reach
"The change in metabolic lifestyle is thought to occur through T cell receptor (TCR)-linked, phosphoinositide 3-kinase (PI3K) and Akt mediated mTOR signaling."

reach
"Akt can then activate mTOR by phosphorylating, and thereby inhibiting, the tuberous sclerosis complex 1/2 (TSC1 and TSC2), allowing Rheb to bind to and activate mTOR [XREF_BIBR]."

reach
"We expected that the reduction in Akt phosphorylation in (ob/ob) hearts lacking one allele of the IGF-1R will reduce mTOR signaling."

sparser
"Being the central node of the PI3K network, AKT activates the mechanistic target of rapamycin kinase complex 1 (MTORC1) via Tuberous sclerosis complex 2 inhibition in the cytoplasm."

reach
"Once activated, Akt activation of the mTOR pathway leads to increased cell proliferation and reduced cell apoptosis involved in the pathogenesis of cancers."

reach
"On the other side of the coin, activation of Akt stimulates the mTor pathway (as well as perhaps inhibiting GR directly, see below) and makes cells resistant [XREF_BIBR]."

eidos
"Akt enables mTOR activity by inactivating TSC1 / 2 through the phosphorylation of TSC2 on several residues , hence enabling Rheb-GTPase to activate mTORC1 ( Figure 1 ; [ 92 ] ) ."

reach
"The PI3K and Akt signaling directly regulates its downstream effect or mTOR, which inhibits autophagy."

reach
"IRS1 972R can phosphorylate and upregulate AKT in a PI3K independent manner, possibly through stress and hypoxia, to activate downstream mTOR pathways to promote cell proliferation and survival XREF_BIBR."

reach
"Activation of P13K induces the phosphorylation of AKT which in turn activates mTOR and its downstream effector molecule p-p70s6kinase."

reach
"The subset of genes both upregulated by Akt and dependent on mTOR activity were associated with estrogen receptor negative status, higher grade, increasing tumor size and poor prognosis in multiple patient cohorts; these associations were either not present or not as strong for the Akt induced, mTOR independent genes or for AKT1 expression alone."

sparser
"Costimulation via CD28 activates PI3K recruiting 3-phosphoinositide-dependent protein kinase-1 and Akt, which, in turn, activates mTOR."

reach
"In this report, we provide evidence that in the presence of glucose, exendin-4 stimulates rodent islet cell DNA replication via the activation of ribosomal protein S6 kinase 1 (S6K1) and that this is mediated by the protein kinase B (PKB)-dependent activation of mTOR complex 1 (mTORC1)."

sparser
"Akt activates the kinase mammalian target of rapamycin (mTOR), which mediates important processes such as cardiac hypertrophy."

reach
"AKT also activates Mammalian target of rapamycin (mTOR) protein kinase, a serine/threonine kinase by phosphorylation [62,63,64]."

sparser
"Through tuberous sclerosis complex 1/2, AKT activates the downstream mTOR, which exists in mTOR complex (mTORC) 1 and mTORC2 respectively [ xref , xref , xref ]."

reach
"We report that expression of a constitutively active form of Akt increases mTOR activity and prevents apoptosis upon AMPK activation."

reach
"Although PI3K activation might decrease SKP2 transcription, and through PKB inactivate TSC2 and activate mTOR, the effects of this pathway on p27 stability are clearly dependent on cell type [XREF_BIBR]."

reach
"To ascertain this hypothesis, the PI3K and Akt pathway activity was evaluated by measuring the expression and activation (phosphorylation) of Akt, the main regulator of this pathway but also by measuring the phosphorylation of natural substrates of Akt; considering that Akt is known to directly activates mTOR [XREF_BIBR], we measured the phosphorylation level of mTOR as an indicator of Akt activity."

reach
"In contrast, over-expression of Akt that also increases mTOR activity prevents autophagy in a non small cell lung carcinoma cell line [XREF_BIBR]."

reach
"AKT activates the mTOR complex 1 (mTORC1) to inhibit autophagy."

sparser
"The regulation of mTOR by LKB1/AMPK signal functionally and mechanistically parallels that of PI3K/AKT signal where AKT activates mTOR via TSC2 ( xref )."

reach
"AFP can activate the PI3K/AKT signalling, stimulates the transcription cofactor mTOR, STAT3, HIF‐1α and Bcl‐2, which regulates the expression of oncogenes, as well as promotes angiogenesis and the growth of the hepatoma cells."

sparser
"AKT can in turn activate mTOR and induce the phosphorylation of the Foxo transcription factors (e.g., Foxo 1 and Foxo 3a) which leads to their nuclear export and subsequent degradation [ xref ]."

sparser
"Akt activates mTOR via direct or indirect phosphorylation."

reach
"MTOR inhibition is known to induce autophagy; however, other signaling pathways are affected directly or indirectly by mTOR inhibition, such as the PI-3K and Akt signaling pathway."

reach
"Increased Akt expression will lead to mTOR activation and increased efficiency of protein translation."

reach
"PI3K is activated by growth receptor signaling at the plasma membrane and activates AKT activating mTOR pathway that inhibits autophagy [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

reach
"In canine adipose derived stem cells, mTOR and p70S6K activation stimulated by PI3K and Akt participates in neuronal differentiation [XREF_BIBR]."

sparser
"Akt signaling depends on a complex relationship with mTOR signaling: Akt activates mTOR complex 1 (mTORC1), while mTORC2 phosphorylate Akt on the hydrophobic motif Ser 473 [ xref ]."

reach
"p70S6k activation by Akt is mediated via the indirect activation of mTOR by Akt."

eidos
"AKT activates mTOR by phosphorylating and inhibiting its negative regulator , the TSC1 / 2 complex ( Inoki et al ., 2002 ) ( Fig 2C ) ."

reach
"HIF-alpha members are also stabilized through the PI3K and AKT pathway that promotes mTOR dependent translation and accumulation of HIF-alpha [10]."

reach
"The phosphorylation ratio for the Akt target mTOR (df = 6; F = 4.18; p < 0.01) increased significantly 2 h and 8 h after refeeding (XREF_FIG)."

reach
"Late-Phase LTP requires MAPK and ERK and PI3 and AKT signaling that activates the mTOR pathway and dendritic protein translation XREF_BIBR."

sparser
"In addition, Akt activates mammalian target of rapamycin (mTOR) and increases protein synthesis via activation of ribosomal protein S6 kinase (S6K) [ xref ]."

sparser
"Although the effect of Ang-(1-7) on mTOR activation was not evaluated in this study, antecedents suggest that mTOR could be activated by Akt, which is activated by Ang-(1-7) via the Mas receptor in skeletal muscle [ xref ]."

reach
"AKT mediated inactivation of the tuberous sclerosis complex (TSC1 and TSC2 proteins) activates mTOR complex 1 (mTORC1, mTOR and Raptor) to upregulate protein biosynthesis required for cell proliferation."

reach
"Sachan et al. claims that inhibition of PI3K/AKT by Afrocyclamin A blocks the mTOR pathway and promotes apoptosis and autophagy in prostate cancer cells (32)."

reach
"AKT activates MTOR by a cascade of phosphorylations, and MTOR inhibits autophagy through the inhibitory phosphorylation of ULK1 (unc-51 like autophagy activating kinase 1) and ATG13, proteins required for autophagy induction."

reach
"Furthermore, rapamycin, a specific inhibitor of mTOR, blocked the activation of mTOR and p70S6K but not PI3K and Akt."

reach
"Akt activation can sequentially activate the downstream mTOR complex1 (mTORC1) and GSK3beta, both of which play important roles in cancer development."

reach
"The RAF/MEK/ERK and PI3K and AKT pathways both activate mTOR signaling, a pathway found to be highly active in neurofibromas."

sparser
"Downstream, PI3K-Akt activates mTOR, which promotes the differentiation of Th1, Th17 and Tfh cells ( xref )."

sparser
"Here we establish an additional pathway by which Akt inhibits TSC2 and activates mTOR."

sparser
"While AKT is activated by phospholipid binding and activation loop phosphorylation at Threonine308 by PDK1 and by phosphorylation within the carboxy terminus at Serine473, mTOR is phosphorylated at Serine2448 via the PI3K-signaling pathway. xref AKT activates the mTOR complex 1 (mTORC1) which in addition to mTOR contains mLST8, PRAS40, and RAPTOR. xref This activation involves phosphorylation of tuberous sclerosis complex 2 (TSC2), which blocks the ability of TSC2 to act as a GTPase-activating protein, thereby allowing accumulation of Rheb-GTP and mTORC1 activation."

reach
"As a member of the PI3K related protein kinase family, mTOR may regulate cell growth and the cell cycle and activated PI3K and Akt activates mTOR."

reach
"Meanwhile, the PI3K and Akt signaling pathway negatively regulates the beclin 1 complex and stimulates mTOR, thereby inhibiting autophagy."

reach
"MTOR activity is stimulated by Akt and ERK 1/2 phosphorylation and inhibited by AMPK phosphorylation."

reach
"PI3K activates AKT, which activates mTOR to prevent cell proliferation and the IkappaB kinase to initiate NF-kappaB activity."

reach
"Although Akt directly activates mTOR and RAPTOR, it may also directly or indirectly activate the p70S6 kinase/4EBP1 pathway this pathway by phosphorylating the tumor suppressor TSC2 XREF_BIBR."

reach
"In addition to the direct phosphorylation of TSC2, Akt activates mTOR also by regulation of cellular energy [XREF_BIBR]."

reach
"Rapamycin directly inhibits mTOR, resveratrol inhibits mTOR through competitive inhibition of ATP binding, and perifosine inhibits the mTOR activator AKT."

sparser
"Upon activation by gene mutation or physiologic receptor stimulation, PI3K recruits AKT, which, in turn, activates its downstream effectors, mTOR and NF-κB, via direct phosphorylation of several mTOR- and NF-κB-pathway components [ xref ], thereby promoting cell survival, proliferation, and anabolic metabolism [ xref , xref ]."

sparser
"Akt may activate mammalian target of rapamycin (mTOR) present in complex 1 (mTORC1), and, in turn, mTORC1 regulates protein synthesis, glucose metabolism, and autophagy."

reach
"To promote protein synthesis and hypertrophy, Akt indirectly activates mTOR while simultaneously inhibiting glycogen synthase kinase 3b (GSK3b)."

reach
"The mTOR pathway that is activated by PI3K and AKT signaling plays a central role in the regulation of cell growth, cell proliferation, and inflammation through downstream transduction of proliferative signals, for example via p70S6 K, RPS6, and HIF-1alpha [XREF_BIBR]."

sparser
"In the canonical IGF-I/AKT/mTOR pathway, AKT activation of mTOR and the subsequent phosphorylation of p70S6K and 4E-BP1 induce protein synthesis."

sparser
"It has been previously reported that AKT and ERK1/2 can activate mTOR (36, 37), and not surprisingly, we observed increased p-ERK1/2Thr202/Tyr204, p-AKTSer473, and p-AKTThr308 levels in AAV9-FGF6–injected muscles (Figure 3F)."

reach
"The results of this study observed that PI3K and AKT were activated and phosphorylated after TAX treatment, and further activated the downstream mTOR and increased the level of its protein expression."

reach
"As Akt, which activates mTOR, negatively regulates high oxidative gene expression by inactivating AMPK (see ' PI3K-Akt-mTOR pathway '), competitive interaction exists between signaling pathways regulating structural and metabolic protein turnover."

sparser
"Similar to the other aforementioned downstream substrates, Akt can activate mTOR indirectly through phosphorylation of Tsc2 (tuberous sclerosis complex 2)."

sparser
"We next examined whether Akt-dependent mTOR activation is involved in adiponectin-induced VEGF-A expression and angiogenesis."

sparser
"PDK-1 might activate AKT, which might directly activate its downstream key protein mTOR."

reach
"These effects were ameliorated by the mTOR inhibitor rapamycin, demonstrating they were due to Akt mediated mTOR activation (Goebbels et al., 2012)."

reach
"MTOR (mammalian target of rapimycyin) increases the surface expression of GLUTs and activates HIF1, and is itself activated by Akt and PI3K."

eidos
"Moreover , under the action of various growth factors , PI3K / Akt can bind to the tyrosine protein kinase receptor to activate mTOR and inhibit autophagy [ 13 ] ."

reach
"33 In Sewall 's study investigating the significance of PIK3CA mutations in HPV associated oropharyngeal SCCs, the authors reported that mutant PIK3CA tumors had a distinct protein expression profile within HPV positive oropharyngeal SCCs, and PIK3CA mutations in HPV positive cells were associated with activation of the mTOR, but not AKT, signaling pathway; and HPV positive cells expressing mutant PIK3CA were more sensitive to PIK3CA and mTOR inhibition versus AKT inhibition, implying that inhibitors for mTOR may have activity against HPV positive PIK3CA mutant oropharyngeal cancers."

reach
"It has been well studied that the PI3K and Akt pathway activates the mTOR signalling that promotes gene expression and protein synthesis [XREF_BIBR], so we postulate that insulin links RBM20 in titin splicing via the PI3K/Akt/mTOR signalling pathway."

reach
"Phosphorylation of Akt at S473 was also increased in DKO thymocytes, indicating enhanced mTOR complex 2 activity."

sparser
"Important downstream effectors of this pathway include Akt, which activates mTOR and appears to affect cell size specifically( xref , xref ), and p70 S6 kinase, which regulates the 40S ribosomal protein S6 to regulate protein synthesis and cell proliferation."

reach
"Thus, while Akt is an upstream activator of mTORC1, Akt is also the target of mTOR via mTORC2."

eidos
"As a downstream effector of Akt , mTOR suppresses autophagy [ 27 , 28 ] ."

sparser
"Akt phosphorylates and activates mTOR, which in turn stimulates key components of the protein synthesis and myoblast differentiation machineries."

reach
"Activation of Akt promotes protein synthesis by activating the mTOR complex and inhibiting GSK3beta."

reach
"Thus, increased phosphorylation of AKT resulted in prevention of nuclear migration of FOXO-3a, triggered the aerobic glycolytic pathway shared by effector cells and activated the mTOR complex pathway (our unpublished data)."

reach
"In turn, activated Akt induces mTOR activity, which leads to the activation of multiple downstream targets, including 4E-BP1 and S6K1."

reach
"Furthermore, FKBP4 can promote Akt and mTOR phosphorylation and activate the Akt and mTOR signaling pathway and an mTOR inhibitor can neutralize the functions of FKBP4 in NSCLC cells."

reach
"As the expression of Mcl-1 is regulated by both transcriptional and posttranslational levels, Akt can trigger its downstream mTOR pathway to enhance Mcl-1 protein translation."

reach
"AKT induces mTOR activity, which promotes glucose metabolism, lipid and nucleotide biosynthesis and protein translation."

reach
"The PI3K-AKT-mTOR axis could be considered to be a single pathway [XREF_BIBR] in which AKT activates mTOR to control cell proliferation and growth in response to environmental stimuli by phosphorylating and inactivating the mTOR suppressors tuberous sclerosis protein 1 (TSC1) and TSC2 [XREF_BIBR, XREF_BIBR]."

reach
"MTOR forms two protein complexes, mTOR complex1, which is activated by the PI3K/AKT pathway, and mTOR complex 2 ."

reach
"In addition, Akt is also reported to activate mTOR and NF-kappaB activation."

reach
"On the other hand, Akt mediated mTOR regulation in colon cancer cells is well established."

reach
"Specifically, insulin induces TSC2 phosphorylation in adult ventricular cardiomyocytes, and the physiological hypertrophic response of NRCMs to T3 thyroid hormone is associated with mTOR activation mediated by AKT."

reach
"Metformin treatment (1) directly (Fig 3-❷), (2) via the inhibition of AKT (Fig 3-❸) and/or (3) activation of AMPK (Fig 3-❹) inhibits the mTOR signaling pathway (Fig 3-❺), thus halting the cellular translational process, which is necessary for the synthesis of host and viral proteins."

reach
"PI3K activation activates Akt which activates mTOR."

reach
"TBK1 plays this role by modulating mTOR, and it is well documented that both DNA (e.g., herpes viruses) and RNA viruses, such as all strains of coronavirus, modulate the mTOR pathway by activation of the PI3K/Akt pathway and/or mTOR itself [43]."

reach
"In this study, we observed that rapamycin inhibited the hypertrophy promoted using AS, which confirmed that Akt mediated mTOR activation by using AS is necessary to induce hypertrophy in myotubes."

reach
"Akt directly and indirectly activates mTOR activity, which then promotes the downstream molecules 4E-BP1 and S6K to enhance cell differentiation, growth, and survival."

reach
"Previous studies have shown that PI3K/AKT and AMPK have opposite effects on the mTOR pathway: inhibition of PI3K/AKT helps to inhibit mTOR pathway, while inactivation of AMPK promotes the mTOR pathway (30,31)."

reach
"Akt activates mTOR through a variety of cellular mechanisms, and thus regulates apoptosis associated proteins [XREF_BIBR]."

reach
"The PI3K and Akt cascade, as part of the insulin response pathway activates mTOR through phosphorylation."

reach
"MTOR lies downstream of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt and PKB), so activated Akt may positively regulate mTOR, leading to increased phosphorylation of ribosomal p70S6 kinase ([MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"There are several ways in which reelin could activate one or more of the mTOR complexes through Akt, which then stimulates mTOR through the tuberous sclerosis complex 1/2 (TSC1/2) and Ras homolog enriched in brain (Rheb), or through Rho and Rac."

reach
"Akt is an upstream activator of mTOR."

reach
"AKT can activate mTOR through the direct phosphorylation of tuberous sclerosis complex 2 (TSC2) [XREF_BIBR]."

reach
"It is of particular interest to further investigate mechanisms by which improvement of Akt signaling mediates antidepressant efficacy in mTOR dependent and -independent manner."

reach
"The phosphatidylinositol-3 kinase and AKT signaling pathway activates mTOR, in turn, directly phosphorylating ribosome protein S6 kinase 1 (S6K1) and eIF4E binding protein 1, both of which are important in the control of protein translation initiation."

reach
"Activated Akt activates mTOR followed by phosphorylation of ribosomal protein S6 kinase (S6K)."

reach
"In addition, the Akt kinase mediates the activation of mTOR, which negatively regulates autophagy."

reach
"As shown in Figure XREF_FIG, upon receiving signals from growth factors and hormones, mTOR is activated by Akt and P13K signalling [XREF_BIBR, XREF_BIBR]."

reach
"The current drugs that specifically target the tyrosine kinase activity of EGFR or selectively inhibit the mammalian target of rapamycin (mTOR), a PI3K and AKT downstream signal transducer showed little efficacy in treatment of primary glioblastoma [XREF_BIBR]."

reach
"Akt positively regulates mTOR (positive flux), and AMPK negatively regulates it (negative flux)."

sparser
"Indeed, IGF-1 treatment is sufficient to cause muscle hypertrophy via Akt activation of mTOR and inhibition of GSK3β ( xref )."

reach
"Akt and Ser (473) P-Akt were detected in ILK immunoprecipitates and small interfering RNA mediated depletion of rictor, but not mTOR, inhibited the amount of Ser (473) P-Akt in the ILK complex."

reach
"Moreover, in IGF-I- and rapamycin treated cells simultaneously deficient in Akt1 and Akt3, p70S6K phosphorylation was not completely eliminated (XREF_FIG), further suggesting an Akt independent activation of mTOR and p70S6K, as well as rapamycin-insensitive activation of p70S6K under conditions of low Akt abundance in myoblasts."

reach
"The serine/threonine protein kinase Akt (protein kinase B) mediates mTOR activity [XREF_BIBR], and positively regulates mTOR."

reach
"Importantly, we found that curcumin reduced Akt, mTOR and P70S6K phosphorylation, effectively suppressing the activity of the Akt and mTOR pathway in HKCs."

reach
"However, increased activity of PI 3-K and Akt signaling may significantly enhance mTOR activity that sometimes limits protective pathways."

reach
"Akt phosphorylated by PI-3K at Ser 473 phosphorylates and inactivates TSC2 and leads to the activation of mTOR [XREF_BIBR]."

reach
"In brief, these authors showed that loss of PTEN results in activated Akt, which in turn activates mTOR."

reach
"40 In the context of the role of PI3K/Akt/mTOR autophagy pathway in oncogenic regulation, Akt as the major player downstream class I PI3K can activate mTOR and lead to inhibition of autophagy."

reach
"To further demonstrate the role of Akt/mTOR dephosphorylation in narciclasine-induced autophagy, we treated gastric cancer cells with insulin (Akt activator) to reactivate Akt/mTOR signaling pathway."
| PMC

reach
"EpCAM participates in CSC phenotypes in vitro and cellular metastasis by enhancing mTOR signalings, such as Akt, mTOR, P70S6K, and 4EBP1 [123], and is also related to survival rate in NPC patients."

reach
"PI3K and Akt signaling also activates the mTOR Complex 1 (mTORC1) in many cellular systems through multiple mechanisms."

reach
"We guess that when cancer cell lines arrest in G2-M by anticancer drugs like paclitaxel, Akt activates mTOR to make cells continue living, then inhibiting mTOR can enhance anticancer effects."

reach
"In this pathway, PI3K increases the cellular content of PI3, which activates Akt; Akt itself then activates mTOR."

sparser
"Akt also activates mTOR, a key regulator of cell growth and proliferation that integrates signaling from insulin and growth factors, amino acid availability, cellular energy status and oxygen levels [ xref , xref ]."

reach
"Further, since AKT positively regulates mTOR activity, we confirmed an elevation of phosphor-mTOR in the lungs of Myr-Akt mice (Figure 3(f), p = 0.029)."

reach
"Both leucine and Akt activate mTOR through phosphorylation of the Ser 2448 site [XREF_BIBR, XREF_BIBR]."

sparser
"Akt activates mammalian target of rapamycin (mTOR), which is deregulated in glioblastoma [ xref ]."

reach
"The activation of mTOR by Akt also promotes fatty acid (FA) uptake and synthesis by activating transcription factor sterol regulatory binding protein 1C (SREBP-1c) which is a protein that enhances the transcription of FA and triglyceride biosynthetic enzymes [XREF_BIBR, XREF_BIBR]."

sparser
"Class I PI3 K activates the serine/threonine kinase Akt, and Akt directly activates mTOR via mTORC1 at S2448 or indirectly through TSC2."

reach
"The PI 3-kinase/Akt pathway promotes cell survival by Akt dependent activation of mTOR, Ikappa-kinase (IKK) and Mdm2, and by inactivation of pro apoptotic Bcl-2 family members such as Bax and Bad and [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"AKT in turn is an activator of mTOR (Hahn-Windgassen et al., 2005)."

reach
"It is well documented that hyperactivation of Akt indirectly increases mTOR activity via inhibitory phosphorylation of TSC2."

reach
"Akt induced activation of mTOR is a key regulator of protein synthesis, since : 1) muscle hypertrophy results in increased mTOR phosphorylation, and 2) mTOR inhibition with rapamycin blocks overload hypertrophy and growth in regenerating muscles."

reach
"PIP3 synthesized by PI3K is able to activate the AkT protein which in turn activates the mTOR transcription factor."

reach
"MTOR signaling is targeted by the PI3K and Akt pathway, the key insulin signaling pathway."

eidos
"Akt activates mTOR by direct phosphorylation , which induces transcription factors associated with growth and cell survival , as well as factors regulating translation initiation , hypoxia , and angiogenesis [ 83 ] ."

reach
"XREF_BIBR - XREF_BIBR Akt indirectly activates mTOR, a complicated checkpoint of cellular growth influenced by growth factor signaling, adenosine monophosphate levels, and nutrient and O 2 availability."

reach
"AKT activates the mTOR containing complex 1 (TORC1) which, via S6K and 4E-BP1, regulates mRNA translation and protein synthesis."

reach
"The activated AKT can promote the activation of mTOR through phosphorylating and inhibiting mTOR upstream repressor tuberous sclerosis complex (TSC) 1/2 complex [XREF_BIBR]."

reach
"Curcumin inhibited Akt phosphorylation in certain cancer cells and has also recently been shown to inhibit mTOR signaling at relatively low concentrations in rhabdomyosarcoma, prostate and breast cancer cells."

reach
"In addition to the activation of mTOR through GSK3 inactivation, Akt has also been reported to activate mTOR signaling by phosphorylation of the TSC complex (consisting of TSC1 and TSC2), which is a major inhibitor of mTOR signaling."

reach
"Direct activation of mTOR by AKT was assessed using a phospho specific antibody directed toward S2448, a phospho-site that correlates with increased mTORC1 activity and up-regulated protein synthesis."

reach
"AKT and PI3K inhibitors both inhibit AKT and mTOR signaling but AKT and mTOR inhibitors activate, whereas PI3K inhibitors inhibit, PI3K activity."

sparser
"Besides this, activation of mTOR by AKT can phosphorylate and inactivate 4E-BP1 (for eIF4E-Binding Proteins), a family of small acidic proteins that function as translational repressors of eIF4E. Phosphorylation of 4E-BP1 by mTOR releases 4E-BP1 from eIF4E thereby activating eIF4E involved translation-initiation complex and consequently the translational repertoire of a cell toward malignancy [ xref ]."

sparser
"Via a cascade: PI3K activation phosphorylates Akt, which activates mTOR."

reach
"Conversely, levels of IGF-I-stimulated p70S6K phosphorylation in cells simultaneously deficient in both Akt1 and Akt3 were increased beyond those seen with loss of any single Akt isoform, suggesting an alternate, Akt independent mechanism that activates mTOR and p70S6K."

reach
"Cytarabine reduced the phosphorylation of the major negative regulator of autophagy, mammalian target of rapamycin (mTOR), and its downstream target p70S6 kinase in REH cells, which was associated with downregulation of mTOR activator Akt and activation of extracellular signal- regulated kinase."

reach
"In T cells, AKT signaling promotes glycolysis by inducing the expression of rate limiting enzymes such as hexokinase and phosphofructokinase and activates mTOR."