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MTOR inhibits IRS1. 41 / 43
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"In addition to diabetes, mTOR/S6K1-mediated feedback inhibition of IRS1 and by extension the oncogenic PI3K/Akt pathway poses drawbacks for cancer therapy and limits the cytotoxic effects of rapamycin-based therapeutic approaches [75]."
32054043
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"Rapamycin has been reported to have alternate effects on Akt phosphorylation; prolonged rapamycin exposure has been shown to inhibit assembly of mTORC2, thereby inhibiting Akt, and mTOR inhibition has also been described to induce insulin receptor substrate-1 (IRS-1), leading to Akt activation."
18701474
signor
"Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten"
11287630
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"In early studies mTOR inhibition led to p70 ribosomal protein S6 kinase (S6K) suppression, IRS1 upregulation, and PI3K-AKT activation 181."
25533673
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"On the other hand, chronic beta-cell hyperfunction, a consequence of excessive leucine exposure, results in accelerated beta-cell apoptosis and eventual secretory deficiency through a negative feedback loop involving the mTOR dependent inhibition of IRS-1 [XREF_BIBR]."
24685128
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"Calorie restriction and/or GH resistance decreases mTOR signaling and phosphoSer inhibition of IRS-1 in skeletal muscle."
19234595
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"Current mTOR inhibition causes the upregulation of the Ras and Raf pathway and inhibition of the negative feedback loop of IRS1 while inhibition of IGF signaling has been shown to inhibit growth and induce death of cancer cells with upregulated PI3K."
24244833
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"One well characterized negative feedback loop involves the tuberous sclerosis complex (TSC), the Rheb RAS superfamily member, the kinase mTOR, and the mTOR target p70 ribosomal S6 kinase (p70S6K) that inhibits insulin receptor substrate 1 (IRS1) and insulin-like growth factor receptor (IGFR) signaling ( xref ; xref ; xref )."
21666717
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"This restoration of IRS-1 mRNA abundance by sustained rapamycin treatment is reversed by actinomycin D (XREF_FIG), indicating that mTOR and S6K1 signaling likely reduces IRS-1 mRNA abundance primarily at the level of gene transcription."
15249583
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"Specifically, mTOR acts through S6 kinase to inhibit IRS-1 (insulin receptor substrate) (Fig. 4C), leading to receptor signal resistance, including insulin resistance that contributes to type 2 diabetes (Blagosklonny, 2006a)."
34990845
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"XREF_BIBR - XREF_BIBR Recent data suggest that the inhibition of mTOR relieves negative feedback regulation of IRS-1, resulting in increased IRS-1 expression and activation of AKT."
19610618
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"For example, mTOR and its downstream S6K can inhibit the upstream insulin signaling molecule IRS-1 to regulate glucose uptake and protein synthesis [XREF_BIBR, XREF_BIBR]."
25792980
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"Interestingly, inhibition of mTOR partially prevented the decrease in IRS1 protein (decrease to 74% compared to control)."
23304509
signor
"Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten"
11287630
signor
"Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten"
11287630
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"UA agonizes signaling of insulin and IGF -1 receptor and elicits AMPK mediated p53 activation, which is abolished by mTOR mediated IRS-1 degradation downstream of IGF-1 receptor signaling [XREF_BIBR]."
28250388
signor
"Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten"
11287630
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"Bose SK, Shrivastava S, Meyer K, Ray RB, Ray R. Hepatitis C virus activates the 32 mTOR/S6K1 signaling pathway in inhibiting IRS-1 function for insulin resistance."
| DOI
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"Inhibition of mTOR has been shown to inhibit proteasomal degradation of IRS-1 enhancing signaling through the PI-3 kinase and Akt pathway."
25104948
eidos
"Specifically , mTOR acts through S6 kinase to inhibit IRS-1 ( insulin receptor substrate ) ( Fig. 4C ) , leading to receptor signal resistance , including insulin resistance that contributes to type 2 diabetes ( Blagosklonny , 2006a ) ."
34990845
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"Thus, the CUL7 E3 appears to be responsible for mediating mTOR dependent degradation of IRS-1, thereby functioning as a critical component of the mTOR and IRS -1 negative feedback loop, which fine-tunes the PI3K activity in accordance with the magnitude and duration of mTOR and S6K activities."
18927510
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"Moreover, the genes up-regulated in Ptch1 +/- / Tis21 KO GCPs include : Depdc6 (Deptor), a subunit of the mTOR complex 1 (mTORC1) that can inhibit this complex and thus relieve the S6K and IRS1 feedback loop; the leucyl-tRNA synthetase Lars, that senses intracellular leucine concentration and initiates molecular events triggering mTORC1 activation, by binding Rraga GTPase; Rraga, a GTPase activator of mTORC1; and Dgkq, which is a mediator of the mTOR complex 2 (mTORC2)."
34395258
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"For example, mTOR and its downstream S6K can inhibit the upstream insulin signaling molecule IRS-1 to regulate glucose uptake and protein synthesis [ xref , xref ]."
25792980
sparser
"Activation of mTOR signaling pathway has been found to suppress insulin sensitivity through serine phosphorylation and the inhibition of IRS1 by mTOR and its downstream effector, S6K1."
18949383
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"MTOR can function in a negative feedback loop and produce glucose intolerance by inhibiting the insulin receptor substrate 1 (IRS-1)."
27127460
signor
"Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten"
11287630
signor
"These results indicate that activation of protein kinase c stimulates a kinase which can phosphorylate insulin receptor substrate-1 at serine 612, resulting in an inhibition of insulin signaling in the cell these data suggest that: 1) activation of pkctheta contributes to ikk and jnk activation by ffas;2) ikk and jnk mediate pkctheta signals for irs-1 serine phosphorylation and degradation; ser-302 phosphorylation is dependent on pi 3-kinase/mtor, whereas ser-307 depends on c-jun nh2-terminal kinase to inhibit irs1 tyrosine phosphorylation. Ser-636 is located around the pi 3-kinase binding site and, therefore, thought to inhibit pi 3-kinase signaling."
9335553
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"MTOR dependent degradation of IRS-1 is required for the initiation of IGF-IR internalization."
29661273
signor
"Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten"
11287630
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"O'Reilly et al. provide evidence that poor tumor response to rapamycins is the result of relieving mTOR mediated feedback inhibition of insulin receptor substrate 1, and activation of Akt mediated survival."
16530700
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"In these cells, Shh upregulates IRS-1 by interfering with mTOR mediated IRS-1 degradation, and by enhancing IRS-1 translation."
24550888
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"For example, mTOR can function in a negative feedback loop and potentially produce glucose intolerance by inhibiting the insulin receptor substrate 1 (IRS-1) [XREF_BIBR]."
31794280
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"A negative feedback loop has been described, whereby mTOR and S6K1 activation attenuates PI3K signaling by suppressing insulin receptor substrate-1 (IRS1) function, a mediator of insulin receptor- dependent activation of PI3K."
19372546
sparser
"By serine phosphorylation and insulin receptor substrate 1 (IRS1) inhibition by mTOR, activation of the mTOR signaling pathway has been shown to reduce insulin sensitivity [ xref ]."
| PMC
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"IRS-1 activity is not reflected by its expression level, which is elevated in mouse embryonic fibroblasts lacking mTORC2 (an mTOR isoform that promotes IRS-1 degradation); IRS-1 signaling capacity was[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25813876
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"This suggests that inhibiting mTOR can promote IRS1 stabilization in CGNPs."
18755774
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"Therefore, mTOR inhibition will induce IRS-1 activation releasing the inhibition mediated by S6K1 and provoking the activation of AKT via an insulin growth factor receptor 1 (IGF-1R) dependent signaling process."
21216931
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"On the other hand, chronic β-cell hyperfunction, a consequence of excessive leucine exposure, results in accelerated β-cell apoptosis and eventual secretory deficiency through a negative feedback loop involving the mTOR-dependent inhibition of IRS-1 [ xref ]."
24685128
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"Although activation of mTOR is necessary and sufficient to induce IRS-1 degradation, our data suggest that the phosphorylation of mTOR did not differ between the two groups."
30275871
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"Mechanistically, PI3K and mTOR inhibition increased IRS1 dependent activation of JAK2 and STAT5 and secretion of IL-8 in several cell lines and primary breast tumors."
23238015
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"Leucine deprivation improves hepatic insulin sensitivity through activating general control nonderepressible 2 (GCN2), which reduces the inhibition of insulin receptor substrate 1 (IRS1) by the mammalian target of rapamycin (mTOR); therefore, enhancing downstream insulin signalling xref ."
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