IndraLab
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"42 However, inhibition of mTOR by some chemicals, such as rapa, will promote AKT phosphorylation by blocking the phosphorylation of insulin receptor substrate 1 and p70 ribosoma S6 kinase, XREF_BIBR, XREF_BIBR which are known to be a part of a negative feedback mechanism of PI3K-AKT signal transduction."
sparser
"Further downstream, mTOR phosphorylates p70 S6 kinase (T389), a regulator of Ribosomal Protein S6 (RPS6) responsible for mRNA translation, and has been proposed to signal via 14-3-3 (tyrosine 3-monooxygenase), a required protein in Raf signaling, to inhibit IRS-1 in a negative feedback loop xref ."
sparser
"Interestingly, the study has also found that autophagy activators decrease the cytotoxicity of fenofibrate, while autophagy inhibitors increase the fenofibrate-induced glioblastoma cytotoxicity including phosphorylation of AMPK and suppression of mTOR- dependent phosphorylation of p70S6K ( xref )."
reach
"In human prostate cancer cells, constitutive expression of HIF-1alpha was found to require signal transduction via phosphatidylinositol-3-kinase (PI3K), AKT (protein kinase B), and the mammalian target of rapamycin (mTOR; also known as FKBP and rapamycin binding protein), a serine/threonine protein kinase that phosphorylates p70 ribosomal protein S6 kinase 1 (S6K1) and the eIF-4E binding protein 1 (4E-BP1), thereby stimulating protein synthesis."
reach
"MTOR complex 1 (mTORC1), an established druggable target against cancer, phosphorylates and controls its substrates p70 ribosomal protein S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) to promote protein translation as well as anabolic metabolism downstream of growth factor receptor activated PI3K-Akt signaling [XREF_BIBR, XREF_BIBR]."
reach
"Here we show that hydrogen peroxide (H 2 O 2), a major oxidant generated when oxidative stress occurs, induced apoptosis of neuronal cells (PC12 cells and primary murine neurons), by inhibiting the mammalian target of rapamycin (mTOR)-mediated phosphorylation of ribosomal p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1)."
reach
"On the basis of high-throughput bioavailability studies of brain bioavailable metabolites after dietary BDPP treatment, we found that select polyphenol metabolites [e.g., cyanidin-3 '- O-glucoside and 3-(3 '-hydroxyphenyl) propionic acid] were able to rescue mTOR and p70S6K phosphorylation in primary cortico-hippocampal neuronal cultures, as well as rescue 4E-BP1 phosphorylation in response to treatment with 4EGI-1, a specific inhibitor of eIF4E-eIF4G interaction."
sparser
"In response to mitogen stimulation, mTOR phosphorylates and activates S6K1, which in turn phosphorylates the 40S ribosomal protein S6, leading to the enhancement of translation of mRNAs with a 5′-terminal oligopyrimidine, including mRNAs that encode for ribosomal proteins and elongation factor-1."
sparser
"To determine whether the nuclear accumulation of ribosomal proteins is dependent on mTOR, we analyzed abundance of the ribosomal proteins S3, S6, and L26 [ xref ] in both nuclear (SENF and RNF) fractions following a potent inhibition of mTOR by pp242 [ xref ] as detected by the mTOR-dependent phosphorylation of S6K1 and Akt (Fig. xref , the lower panel)."
reach
"The activation of mTOR is supported by increased phosphorylation of upstream proteins including ERK and Akt, and mTOR then phosphorylates and activates the downstream protein p70S6K, which inhibits eEF2K, thereby decreasing the phosphorylation of eEF2 and effectively inhibiting eukaryotic initiation factor 4E (eIF4E)."
reach
"ROS triggered PI3K activation can transduce oncogenic AKT-mTOR signaling; mTOR can increase the phosphorylation of both eukaryotic initiation factor 4E binding protein1 (4EBP-1) and S6K1, leading to the translation and expression of mRNAs encoding several major anti-apoptotic proteins including XIAP, c-IAP1, Bcl-XL, and BCl-2 [XREF_BIBR]."
sparser
"The phosphorylation of S6K1 by mTOR is confined to a single residue (T389)( xref ), and this phosphorylation was eliminated by pemetrexed ( xref ), whereas four residues on 4EBP1 are phosphorylated by mTOR ( xref ); the broader migration pattern seen in pemetrexed-treated cells with the pan-4EBP1 antibody ( xref ) suggests that several of these phosphorylation sites are affected by drug."
reach
"AZD8055 (XREF_FIG) is a prototypic, orally-available, ATP-competitive mTOR kinase inhibitor, that suppresses phosphorylation of the mTORC1 substrates p70S6K and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), as well as phosphorylation of the mTORC2 substrate AKT (S473)."
rlimsp
"Three of these sites are highly conserved among AGC kinases (cAMP dependent Protein Kinase, cGMP dependent Protein Kinase, and Protein Kinase C subfamily): the activation loop in the kinase domain, and two C-terminal sites, the turn motif and the hydrophobic motif. The common dogma has been that phosphorylation of the hydrophobic motif primes S6K1 for the phosphorylation at the activation loop by phosphoinositide-dependent protein kinase 1 (PDK1). Here, we show that the turn motif is, in fact, phosphorylated first, the activation loop second, and the hydrophobic motif is third. Specifically, biochemical analyses of a construct of S6K1 lacking the C-terminal autoinhibitory domain as well as full-length S6K1, reveals that S6K1 is constitutively phosphorylated at the turn motif when expressed in insect cells and becomes phosphorylated in vitro by purified PDK1 at the activation loop. Only the species phosphorylated at the activation loop by PDK1 gets phosphorylated at the hydrophobic motif by mammalian target of rapamycin (mTOR) in vitro."
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"Activated PI3K and Akt may positively regulate mTOR, which further causes phosphorylation of ribosomal p70 S6 kinase 1 (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]."
sparser
"Further, immobilization results in an attenuated response to leucine, shown through reduced phosphorylation of P70S6K. Complete phosphorylation of P70S6K1 by mTOR requires phosphorylation by PDK1 and has recently been suggested to be proceed that of mTOR (Keshwani et al . xref , Kelleher et al . xref ), yet the order in which these occur is still up for debate [discusses in Magnuson et al . ( xref )]."
sparser
"MTOR
phosphorylates the p70 ribosomal S6 kinase (p70S6K) leading to
phosphorylation of the ribosomal protein S6, which stimulates mRNA
translation rates. xref Antibodies
that recognize phosphorylated S6 (Ser240/244) are widely
accepted functional readouts of mTOR activity. xref Therefore, to establish whether RGC dendritic
retraction correlates with changes in mTOR activity in these neurons, we
examined phospho-S6 (Ser240/244) expression in intact and
axotomized retinas."
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"Anabolic pathways that promote fiber hypertrophy result in activation via phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR), which leads to phosphorylation and activation of p70 S6 kinase (p70S6K) that in turn phosphorylates the ribosomal protein S6 [33]."
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"Inhibition of mTOR by microinjection of rapamycin locally into the IC reduced expression of eEF1A and post-synaptic density protein 95 (PSD-95), reduced S6K1 phosphorylation, and increased eEF2 phosphorylation; at the same time, this inhibition of mTOR in the IC attenuated long-term taste memory as analyzed by LI-CTA paradigm [XREF_BIBR]."
sparser
"Mammalian target of rapamycin (mTOR) is a master regulator of autophagy and phosphorylates p70S6K. 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 xref ."
reach
"Here we show that hydrogen peroxide (H 2 O 2), a major oxidant generated when oxidative stress occurs, induced apoptosis of neuronal cells (PC12 cells and primary murine neurons), by inhibiting the mammalian target of rapamycin (mTOR)-mediated phosphorylation of ribosomal p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1)."
rlimsp
"We found that overexpression of 4EBP1 promoted the apoptosis rate as well as the VP1 expression after viral infection, and overexpression of p70S6K promoted apoptosis while decreased the VP1 expression at 24 h p. i. Activated mTOR phosphorylates the downstream effectors 4EBP1 and p70S6K."
rlimsp
"Consistent with prior studies that have demonstrated that EPO increases mTOR signaling in inflammatory cells [27], [33] and in osteoblastic phenotypes in human bone marrow stromal cells [34], we illustrate that EPO in neuronal cells requires mTOR to phosphorylate p70S6K and 4EBP1."
sparser
"Western blot analysis showed significantly increased levels of phosphorylated mTOR (p-mTOR) and phosphorylated p70S6 kinase 1 (p-S6K1, a downstream effector of mTOR) in the ipsilateral L4/5 spinal cord 2h, 1 day, 3 days, and 7 days after intraplantar CFA injection and in the ipsilateral L4/5 dorsal root ganglions (DRGs) 1 and 3 days after CFA injection."
rlimsp
"In the present study, we observed that increased insulin levels may have resulted in increased mTOR levels and phosphorylation of p70S6K; however, we have no data that directly address this idea, and previous studies [30,34] do not support the idea that typical fasting insulin concentrations (above basal levels) can stimulate the mTOR/p70S6K pathway."
sparser
"We found that the expressions of mTOR and S6K in the liver (Figure xref d) were not obviously changed by Dex exposure or Dex exposure with Sar or/and CDP treatment, whereas Ser 2448 phosphorylation of mTOR, and Thr 389/412 phosphorylation of p70S6K (Figure xref d) were upregulated markedly by Dex exposure, both of which were abolished significantly by Sar or CDP treatment, and abolished further by the co‐treatment, showing a synergistic effect between Sar and CDP."
reach
"Now that aberrant activation of mTOR and p70S6K pathway plays an important role in tumorigenesis and phosphorylated p70S6K by mTOR has higher activity to promote translation than p70S6K [XREF_BIBR, XREF_BIBR], we speculated the combination of mTOR inhibitor and p70S6K siRNA could inhibit mTOR and p70S6K pathway at the most extent and thus inhibit tumor growth better."
reach
"Seminal studies have shown that phosphorylated AKT induces mTOR mediated phosphorylation of p70S6K in skeletal muscle,62 resulting in muscle hypertrophy.63 The increased insulin stimulated p-p70S6K in gastrocnemius with Fst288 overexpression even though p-AKT was not significantly increased could be explained by signal amplification downstream of Akt, as p70S6K activity previously has been shown to be preserved in mice muscle with severe insulin receptor defects,64 suggesting either signal amplification or another upstream kinase regulating p70S6K in response to insulin."
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"The phosphorylation of Akt by mTOR complex 2 (mTORC2) results in full activation of this kinase [XREF_BIBR], which then activates the mTOR complex 1 (mTORC1) to phosphorylate S6K1 and dissociate 4EBP1 (eukaryotic translation initiation factor 4E binding protein 1) from the initiation factor [XREF_BIBR]."
sparser
"Activated mTOR phosphorylated p70S6K, which induces GBM formation in mice. xref S6K1 correlated with Ki67 labeling index, indicating that p-p70S6K is correlated with proliferation of tumor cells. xref After WB assay, we confirmed that cytarabine significantly decreased phosphorylation of p70S6K in a dose-dependent manner."
reach
"In MAC-T cells, ATRA increased the mRNA levels of alpha S1 -casein and beta-casein, janus kinase 2 (JAK2) and E74 like factor 5 of the signal transducer and activator of transcription 5 beta (STAT5-beta) pathway, ribosomal protein S6 kinase beta-1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 of the mammalian target of rapamycin (mTOR) pathway, inhibited the mRNA expression of phosphoinositide 3-kinase and eukaryotic initiation factor 4E of the mTOR pathway, and promoted the phosphorylation of STAT5-beta and S6K1 proteins."
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"By binding to FK binding protein 12, it inhibits the functioning of a specific cell regulation protein of cell growth, the mammalian target of rapamycin (mTOR), which causes reduced phosphorylation of p70 S6 kinase further down the signal transduction pathway [XREF_BIBR - XREF_BIBR]."
reach
"In addition, mTOR, another substrate subjected to phosphorylation by AKT, enhances phosphorylation of S6K1 and 4E-BP1 [XREF_BIBR] and plays crucial roles in the regulation of ribosomal protein synthesis, for example, production of cyclin D1 and VEGF-A at both transcriptional and translational levels [XREF_BIBR, XREF_BIBR]."
reach
"We found that overexpression of 4EBP1 promoted the apoptosis rate as well as the VP1 expression after viral infection, and overexpression of p70S6K promoted apoptosis while decreased the VP1 expression at 24h p. i. Activated mTOR phosphorylates the downstream effectors 4EBP1 and p70S6K."
reach
"In addition, mTOR, another substrate subjected to phosphorylation by Akt, enhances phosphorylation of S6K1 and 4E-BP1 and plays a crucial role in the regulation of ribosomal protein synthesis, for example, production of cyclin D1 and VEGF-A at both the transcriptional and translational levels XREF_BIBR."
reach
"This allows the formation of an active TSC1 and TSC2 dimer that inhibits the phosphorylation of Ribosomal Protein S6 Kinase B1 (RPS6KB1) by the mTOR protein complex, which in turn inhibits the phosphorylation of Ribosomal Protein S6 (RPS6), part of the 40S ribosomal subunit required for initiation [XREF_BIBR]."
sparser
"SESN2 inhibits mTOR-dependent phosphorylation of p70S6K and 4E-BP1,( xref )and knockdown of SESN2 resulted in the activation of mTOR signaling indicating that the important role of SESN2 on mTOR inhibition.( xref )Our results from western blotting demonstrated that mTOR was down-regulated by fisetin treatment in HNCCs consistent with other previous studies showing tumor inhibiting potentials of fisetin through mTOR pathway.( xref , xref , xref )These results suggest that fisetin-induced apoptotic potentials is through SESN2/mTOR signaling axis."
reach
"Interestingly, the study has also found that autophagy activators decrease the cytotoxicity of fenofibrate, while autophagy inhibitors increase the fenofibrate induced glioblastoma cytotoxicity including phosphorylation of AMPK and suppression of mTOR- dependent phosphorylation of p70S6K."
sparser
"Now that aberrant activation of mTOR/p70S6K pathway plays an important role in tumorigenesis and phosphorylated p70S6K by mTOR has higher activity to promote translation than p70S6K [ xref , xref ], we speculated the combination of mTOR inhibitor and p70S6K siRNA could inhibit mTOR/p70S6K pathway at the most extent and thus inhibit tumor growth better."
reach
"In response to mitogen stimulation, mTOR phosphorylates and activates S6K1, which in turn phosphorylates the 40S ribosomal protein S6, leading to the enhancement of translation of mRNAs with a 5 '-terminal oligopyrimidine, including mRNAs that encode for ribosomal proteins and elongation factor-1."
sparser
"Phosphorylation of S6K1 on Thr390 (human Thr389) is a primary activator of its kinase activity and appears to regulate translation of ribosome-related transcripts and ribosome biogenesis, although the mechanism underlying differential regulation of phosphorylation of Eif4ebp1 and S6K1 by Frap1 is currently unknown xref ."
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"MGluR activation of PI3K, mTOR and ERK also stimulates phosphorylation of p70 ribosomal S6 kinase (RSK) and ribosomal S6 in hippocampal slices which functions to increase translation of a subset of mRNAs (those with a 5 ' terminal oligopyrimidine tract; 5 ' TOP) that encode ribosomes, translation factors, thus increasing the overall translational capacity of the neuron."
sparser
"During viral translation NS5A activates m ammalian t arget o f R apamycin (mTOR) pathway by disrupting the interaction between FK506-binding protein 38 (FKB38) and mTOR. xref , xref Activated mTOR initiates phosphorylation of ribosomal protein S6 kinase beta-1 (S6K1) protein, which eventually phosphorylates ribosomal protein 6 (rps6). xref Expression of NS5A increases the level of phosphorylated pS6K1."
reach
"The phosphorylation of S6K1 by mTOR is confined to a single residue (T389), and this phosphorylation was eliminated by pemetrexed (XREF_FIG), whereas four residues on 4EBP1 are phosphorylated by mTOR; the broader migration pattern seen in pemetrexed treated cells with the pan-4EBP1 antibody (XREF_FIG) suggests that several of these phosphorylation sites are affected by drug."
reach
"When BCAA levels are sufficient, mTOR is activated and causes an increase in p70S6K phosphorylation, subsequently activating the S6 ribosomal protein, thereby inducing protein synthesis.9, 10 In contrast, at low BCAA concentrations, mTOR recognizes the limited substrate availability for protein synthesis and recycling and inhibits p70S6K phosphorylation, hindering normal protein recycling, and thus allowing ' wear and tear ' protein damage to accumulate."
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"Activated PI3K and Akt may positively regulate mTOR, which further causes phosphorylation of ribosomal p70 S6 kinase 1 (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
"We found that AKT and mTOR signaling was significantly inhibited in the MMQ and GH3 cells by CAB in a time dependent manner as indicated by decreased phosphorylation of AKT and mTOR as well as decreased phosphorylation of p70S6K and 4EBP1, two key downstream effectors of the mTOR pathway."
sparser
"In addition, mTOR, another substrate subjected to phosphorylation by Akt, enhances phosphorylation of S6K1 and 4E-BP1 and plays a crucial role in the regulation of ribosomal protein synthesis, for example, production of cyclin D1 and VEGF-A at both the transcriptional and translational levels xref ."
reach
"4E-BP1 and S6K1 are phosphorylated by mammalian target of rapamycin complex 1 (mTORC1) which regulates the binding of eIF4E to the mRNA 5 ' cap through phosphorylation of 4E-BP1 and stimulates protein synthesis through the phosphorylation of S6K1 XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR."
sparser
"In addition, mTOR, another substrate subjected to phosphorylation by AKT, enhances phosphorylation of S6K1 and 4E-BP1 [ xref ] and plays crucial roles in the regulation of ribosomal protein synthesis, for example, production of cyclin D1 and VEGF-A at both transcriptional and translational levels [ xref , xref ]."
sparser
"Activated mTOR phosphorylates the downstream effectors 4EBP1 and p70S6K. Being responsible for the cap-dependent translation of mRNA and the protein synthesis, they are critical components in a pathway regularly co-opted by viruses to ensure translation of their own mRNA. xref , xref Our previous work has shown that CVB3 infection can activate mTOR/4EBP1 pathway to promote the synthesis and release of the viral protein. xref In this study, CVB3 infection directly stimulated PI3K/Akt pathway, keeping the mTOR/4EBP1 pathway activating."
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"The mTOR pathway, a significant controlling factor for MPS, stimulates the kinase activity of the complex and leads to the phosphorylation of 4E-BP1 and p70S6K, which are two enzymes that also modulate protein synthesis at the level of mRNA translation initiation [XREF_BIBR, XREF_BIBR]."
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"The involvement of mTOR signaling in fibroblast proliferation is also supported by our finding that FGF2, a growth factor that activates mTOR signaling [55,56], induced the phosphorylation of PS6K and increased fibroblast proliferation.The activation of mTOR signaling induces protein synthesis by translating genes responsible for cell growth and proliferation."
| PMC
sparser
"ROS-triggered PI3K activation can transduce oncogenic AKT-mTOR signaling; mTOR can increase the phosphorylation of both eukaryotic initiation factor 4E-binding protein1 (4EBP-1) and S6K1, leading to the translation and expression of mRNAs encoding several major anti-apoptotic proteins including XIAP, c-IAP1, Bcl-XL, and BCl-2 [ xref ]."
sparser
"Under the condition of stimuli, PI3K phosphorylates PIP2 to create PIP3 and recruits AKT to the plasma membrane to active PDK1 and mTOR complex which phosphorylates 4E-BP1 and p70 ribosomal S6 kinase that trigger ribosome biogenesis and translation in cell growth and division [ xref , xref ] ( Figs. xref & xref )."
sparser
"It is reported that mTOR activation is the mechanism of 5-HT-induced hepatic steatosis and IR mediated by 5-HT 2 R in the liver and adipocytes xref , xref , so we examine LTS or 5-HT-indueced activation of hepatic mTOR and S6K, a downstream target of mTOR, by detecting Ser 2448 phosphorylation of mTOR, and Thr 389/412 phosphorylation of p70S6K."