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AKT1S1 activates MTOR. 52 / 52
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"Torin2 eradicated drug-resistant tumor cells, inhibited the phosphorylation of PRAS40 and effectively inhibited the downstream effectors of the mTOR pathway (4E-BP1 and S6K)."
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"PRAS40 phosphorylation by Akt and association with 14-3-3, a cytosolic anchor protein, are crucial for insulin to stimulate mTOR providing PRAS40 as an important regulator of insulin sensitivity and a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In addition, metformin suppressed the proliferation of glioma cells through PRAS40 mediated mTOR inhibition independent of AMPK [XREF_BIBR]."
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"We propose that active GSK3α/β cooperates with mTOR activator PRAS40 or p70 s6 kinase for the regulation of AKT/mTOR signaling pathway, and altogether these regulators inhibit autophagy by inhibition of AKT and restriction of mTOR activation."
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"While the first phosphorylation event is supposed to activate mTOR by inhibition of the upstream GTPase-activating protein complex TSC1/2, phosphorylation of pRAS40 at T246 leads to its dissociation from the mTORC1 complex and the cessation of its inhibitory activity on mTOR kinase [14, 25]."
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"In a recent report, inhibition of mTOR signalling by the overexpression of PRAS40 prevented the development of cardiomyopathy in high-fat diet fed mice [XREF_BIBR]."
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"We found that increased phosphorylation of proline-rich Akt substrate of 40 kDa (PRAS40) can activate the mTOR pathway and inhibit autophagy [19]."
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"Following phosphorylation of PRAS40 by Akt, PRAS40 can dissociate from mTORC1 to promote mTOR activation and prevent apoptosis."
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"Akt mediated phosphorylation of PRAS40 induces mTOR activation XREF_BIBR."
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"It inhibits the proline-rich AKT substrate of 40 kDa (PRAS40) and tuberous sclerosis complex 2 (TSC2) through inhibition of the GTPase activity of the TSC1/TSC2 complex, thereby activating mTOR complex 1 (mTORC1) through the RAS homologue enriched in brain (RHEB) (117, 118)."
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"AKT1S1 can activate mammalian target of rapamycin (mTOR)—mediated signaling pathways when phosphorylated, 75 and mTOR signaling was observed to have higher activity in AD brains."
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"Upon phosphorylation, PRAS40 dissociates from the mTOR complex and increases mTOR kinase activity."
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"Under some circumstances, studies suggest that over-expression of PRAS40 that simultaneously activates Akt and mTOR but blocks forkhead transcription factor activity can lead to neuronal protection during ischemic induced oxidative stress ( xref )."
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"In summary, our study identifies that phosphorylation of PRAS40 may lead to the activation of mTOR signaling pathway in CNI induced rapid progression of human renal cancer."
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"Furthermore, PRAS40 phosphorylation by Akt and association with 14-3-3, a cytosolic anchor protein, are crucial for insulin to stimulate mTOR."
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"Intriguingly, while the levels of p-AKT (serine 473) remained unchanged, the levels of p-GSK3beta, p-PRAS40 and p-AKT substrates increased markedly in L-Atg5 and mTOR DKO livers (XREF_FIG)."
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"We speculated that the down-regulation of AKT1S1 may increase the activity of mTOR complex 1, thereby resulting in SONFH.All of BACH1, MGST1 and SETD1B were positively correlated with osteoclast differentiation."
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"Our studies highlight EPO and PRAS40 signaling in the mTOR pathway as potential therapeutic strategies for development against degenerative disorders that lead to cell demise."
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"Some of these proteins that mediate mTOR signaling such as Raptor, Rictor, PRAS40, mSin1, FKBP38, and IRS-1 may represent therapeutic targets affected by the recent development of small molecule mTOR [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"It has been reported that CNI treatment activates the proto-oncogene Ras [49] and promotes the phosphorylation of PRAS40 (negative regulator of mTORC1) to increase mTOR activity [50]."
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"PRAS40 phosphorylation promotes the activation of mTOR signaling pathway."
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"Binding of PRAS40 to the mTORC1 signaling complex attenuates mTOR ac-tivity, presumably by inhibition of downstream substrate binding; however, phosphorylation of the Thr246 residue by Akt and PKB rel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"PRAS40 increases the activation of mTOR pathway in ESFT cells and glomerular mesangial cells [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"Silencing of PRAS40 by small interfering RNA suppresses the mTOR pathway signaling in response to insulin treatment in HEK293 cells, adipocytes, liver cancer cells and ESFT cells [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"PRAS40 phosphorylation by Akt is critical for insulin to stimulate mTOR, leading to protein synthesis and cell growth."
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"AKT1S1 can activate mammalian target of rapamycin (mTOR)–mediated signaling pathways when phosphorylated, and mTOR signaling was observed to have higher activity in AD brains, suggesting a role of AKT1S1 in the accumulation of Aβ and tau proteins."
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"In contrast, other studies have reported that PRAS40 is essential to induce mTOR activity, and that silencing PRAS40 impairs the phosphorylation of 4E-BP1 and S6, two of mTOR 's downstream proteins."
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"AKT1 is one of the downstream targets of PIK3, which phosphorylates AKT1S1 and relieves AKT1S1 mediated MTOR inhibition 60."
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"Most importantly, Torin2 eradicated drug-resistant tumor cells, inhibited the phosphorylation of PRAS40 and effectively inhibited the downstream effectors of the mTOR pathway (4E-BP1 and S6K)."
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"For instance, protein levels of p-P70S6K and p-S6 in the mTOR pathway were shown to be decreased in PRAS40 KO mice (XREF_FIG), but these two proteins were not examined in PRAS40 transfected brains, even though we have shown that PRAS40 vector transfection promoted mTOR activity (XREF_FIG)."
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"In fact, the observed decreases in eIF4E and several other proteins necessary for mTOR signaling such as Raptor, PRAS40, cyclin D1, and stearoyl CoA desaturase (SCD) a key enzyme in fatty acid synthesis, suggest reduction in mTOR associated cell proliferation and growth [XREF_BIBR, XREF_BIBR]."
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"Phosphorylated PRAS40 could strongly activate mTOR which is also known as the PRAS40-Akt-mTOR signal pathway ( xref )."
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"Although Akt has many substrates within the cell, phosphorylation of two substrates, TSC2 and PRAS40, leads to activation of mTOR."
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"PRAS40 knockdown could inhibit the activities of the mTOR pathway; moreover, neuronal autophagy and apoptosis were exacerbated by PRAS40 knockdown."
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"More recently, Vander Haar et al. identified an mTORC1 binding partner called PRAS40 (protein-rich Akt/PKB substrate 40 kDa) which mediate Akt signals to mTOR and negatively regulate its activity [11][MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"1 PRAS40 is known to inhibit mammalian target of rapamycin C1 (mTORC1) activity by binding Raptor and competing away binding of the mTOR substrates 4E-BP1 and p70S6K."
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"PRAS40 KD increased the association of mTOR with p-raptor (XREF_FIG)."
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"Phosphorylation of PRAS40 has been shown to decrease autophagy and promote mTOR activation after status epilepticus ( Lin et al., 2020 )."
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"The induced phosphorylation of PRAS40 has been posited to increase mTOR activity [XREF_BIBR; XREF_BIBR]."
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"By phosphorylating and deactivating a 40 kDa proline-rich AKT substrate (PRAS40) and tuberculosis 2 (TSC2), phosphorylated AKT stimulates the mammalian rapamycin target (mTOR) (45)."
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"When viewed in this light, our results suggest that phosphorylation of PRAS40 at T246 may not be essential, or at least not sufficient to positively regulate mTOR activity and protein synthesis."
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"Phosphorylation of PRAS40 by Akt can block the activity of this substrate, lead to its dissociation from mTORC1 to promote mTOR activation and prevent apoptosis."
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"Thus, the regulatory interactions among PRAS40, mTOR, and mTOR substrates and the mechanism whereby PRAS40 promotes the activity of mTOR during cerebral ischemia require further elucidation.As a downs[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The phosphorylation of PRAS40, either via AKT or mTOR, leads to its dissociation from mTORC1, which is released and active [20]."
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"They both also phosphorylate proline rich-Akt substrate 40 (PRAS40) increasing mTOR kinase activity ( Aziz et al., 2018 )."
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"Given these data and the role of PRAS40 in insulin signaling, it is tempting to speculate that Abeta accumulation increases PRAS40 phosphorylation, which in turn leads to chronic hyperactive mTOR and [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The mTOR activity, mediated by the proline-rich AKT substrate 40 (PRAS40), is increased in cell lines transfected with mutant amyloid precursor protein (APP), and in brains of 3xTg-AD mice, an animal [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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 the P53/PRAS40/mTOR pathway, one of the important components of the mTOR complex is the proline-rich Akt and substrate PRAS40, which is at downstream of Akt, and the phosphorylated PRAS40 (pPRAS40) can activate the mTOR pathway (Kovacina et al., 2003; Wiza et al., 2014)."
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"Both kinases phosphorylate proline rich-AKT substrate 40 (PRAS40), which increases mTOR kinase activity on dissociation from mTORC1."
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"We have characterized the effect of both prodiginines on critical elements of mTOR signaling such as AKT, PRAS40, p70 S6K and 4E-BP1, as well as on different compensatory mechanisms which link PI3K/mT[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Several substrates overlap with AKT and mTOR signaling, including PRAS40 [XREF_BIBR], TSC2 [XREF_BIBR], 4EBP1 [XREF_BIBR], and EIF4B [XREF_BIBR - XREF_BIBR]."
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