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phosphosite cbn pc11 biopax bel_lc signor biogrid tas lincs_drug hprd trrust | geneways tees isi trips rlimsp medscan sparser reach
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MTOR phosphorylates IRS1. 10 / 46
| 2 14 29
reach
"IRS1 is phosphorylated at S636/639 by the mTOR pathway [XREF_BIBR], keeping it from activating RTKs and further activating the PI3K pathway."
reach
"Statins also induced mTOR dependent phosphorylation of insulin receptor substrate 1."
sparser
"In contrast, sustained PI3K/Akt activation inhibits IRS1 activity by negative feedback through the activation of mTOR and p70S6K that phosphorylate IRS1 on its inhibitory domain (Ser 307 ) [ xref ]."
reach
"Although S6K1 is an effector of growth, recent reports show that amino acids also negatively affect insulin signaling through mTOR and S6K1 phosphorylation of IRS1."
sparser
"Physiologic activation of the Akt pathway is regulated, in part, by a negative feedback loop involving phosphorylation of insulin receptor substrate 1 (IRS1) by the mTOR effector molecule S6 kinase 1 ( xref A) [ xref – xref ]."
sparser
"mTOR induced the serine phosphorylation of IRS-1 (Ser-636/639), and such phosphorylation was inhibited by rapamycin."
reach
"Increased BCAAs may increase activation of mTOR and S6K1 kinase pathway, which phosphorylates insulin receptor substrate 1 (IRS-1), with a subsequent decline in IRS-1 associated phosphatidylinositide 3-kinase (PI 3-kinase) activity."
reach
"In their pioneering study, Pan and colleagues XREF_BIBR reported that Cul7 ubiquitinates IRS-1 and that phosphorylation of IRS-1 by mTOR and S6K is important for Cul7 recognition of IRS-1."
reach
"Here, we demonstrate that nutrients suppress phosphatidylinositol 3 (PI3)-kinase/Akt signaling via Raptor dependent mTOR (mammalian target of rapamycin)-mediated phosphorylation of insulin receptor substrate 1 (IRS-1)."
reach
"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."
MTOR phosphorylates IRS1 on serine. 10 / 20
| 1 1 1 17
reach
"Other feedback or alternative signaling loops that mediate resistance involve an mTOR dependent serine phosphorylation of insulin receptor substrate-1 (IRS-1) that enhances insulin like growth factor-1 (IGF-1) signaling leading to downstream activation of PI3K and AKT."
rlimsp
"The activation of mTOR phosphorylates its downstream protein ribosomal S6 protein kinase (S6K), participating in several processes including protein synthesis and proliferation [12], [13]. It became apparent that serine phosphorylation of IRS1 reduces the ability of IRS1 to activate PI3K [10]–[12]."
reach
"mTOR induced the serine phosphorylation of IRS-1 (Ser 636/639), and such phosphorylation was inhibited by rapamycin."
reach
"TNF-alpha produced by obesity induced inflammation stimulates IKK XREF_BIBR, JNK XREF_BIBR, and mTOR and S6K XREF_BIBR XREF_BIBR, which enhance serine phosphorylation of insulin receptor substrate-1 (IRS-1)."
reach
"Recent studies demonstrate that the mTOR downstream target S6K1 directly phosphorylates IRS1 serine residues, including Ser 302/307, Ser 307/312, Ser 632/636, and Ser 1097/1101."
reach
"In a similar fashion, it was shown that rapamycin induced mTOR inhibition decreased the serine phosphorylation of IRS-1, which was associated with a compensatory IGF-I downstream signaling via the PI3K and AKT pathway [XREF_BIBR]."
reach
"Studies conducted in rodent models and cultured rat myocytes found that increased exposure of skeletal muscle cells to BCAA impairs insulin action in concert with activation of the mammalian target of rapamycin (mTOR), which causes serine phosphorylation of insulin receptor substrate-1 and disrupts insulin signaling."
reach
"Overfeeding and metabolic stresses, including high levels of free fatty acids or inflammatory cytokines, enable activation of a number of endogenous protein kinases, such as mTOR, JNK, and IKKbeta, which can phosphorylate IRS1 and IRS2 at serine and threonine residues and which mediate IRS protein ubiquitination and degradation, resulting in insulin resistance [XREF_BIBR]."
reach
"The mammalian target of rapamycin (mTOR) is downstream of Akt and can phosphorylate IRS1 on serine residues, targeting it for degradation."
trips
"mTOR induced the serine phosphorylation of IRS-1 (Ser-636/639), and such phosphorylation was inhibited by rapamycin."
MTOR phosphorylates IRS1 on S307. 10 / 13
2 | 1 10
reach
"Although the direct phosphorylation sites targeted by mTOR and p70S6 kinase are disputed XREF_BIBR, inhibition of mTOR by rapamycin significantly reduces phosphorylation of IRS-1 residues S302, S307 and S318 XREF_BIBR."
sparser
"This result prompted us to examine whether IKKβ-derived phosphorylation of TSC1 can serve as a switch for TNFα- and mTOR-induced phosphorylation of IRS1 at Ser307 and Ser636/639."
reach
"mTOR and its downstream effector S6K1 suppress IRS1 activity by directly phosphorylating IRS1 at Ser636 and Ser639 and Ser307, respectively, which leads to desensitization of insulin signaling."
reach
"Recent studies demonstrate that the mTOR downstream target S6K1 directly phosphorylates IRS1 serine residues, including Ser 302/307, Ser 307/312, Ser 632/636, and Ser 1097/1101."
reach
"Furthermore, the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented the osmotic shock induced phosphorylation of IRS-1 on Ser307."
reach
"mTOR being a central regulator of amino acid and insulin signaling, under amino acid abundance, it phosphorylates IRS1 (at serine 307) and inhibits the downstream insulin signaling."
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"
reach
"Recent studies demonstrate that the mTOR downstream target S6K1 directly phosphorylates IRS1 serine residues, including Ser 302/307, Ser 307/312, Ser 632/636, and Ser 1097/1101."
reach
"Short-term osmotic stress induces the phosphorylation of IRS-1 on Ser307 by an mTOR dependent pathway."
reach
"The findings of the present study of diet-and obesity induced insulin resistance in murine models suggest that suppression of TSC1 by IKKbeta activates mTOR and S6K1, which in turn phosphorylate IRS1 at Ser636/639 and Ser307, thereby inhibiting IRS1 function)."
MTOR phosphorylates IRS1 on S636. 10 / 12
1 | 1 1 9
reach
"mTOR and its downstream effector S6K1 suppress IRS1 activity by directly phosphorylating IRS1 at Ser636 and Ser639 and Ser307, respectively, which leads to desensitization of insulin signaling."
reach
"These include mammalian target of rapamycin (mTOR)-mediated phosphorylation of IRS1 serine 636 (Ser636) and serine 639 (Ser639), ribosomal S6 kinase 1 (S6K1)-mediated phosphorylation of IRS1 serine 307 [Ser307 (mouse serine 302) (Ser302)] and serine 1101, IkappaB kinase beta (IKKbeta) - and c-Jun N-terminal kinase (JNK)-mediated phosphorylation of IRS1 serine 312 [Ser312 (mouse Ser307)], and protein kinase zeta mediated phosphorylation of IRS1 serine 323 (mouse serine 318)."
reach
"mTor signaling leads to phosphorylation of IRS-1 on serine 636, which serves as a negative feedback loop to decrease activation of the PI3K and Akt pathway."
reach
"Since IRS-1 Ser636 phosphorylation is increased by mTOR activation, the investigators proceeded to demonstrate that nicotine acutely increases mTOR activation in cultured myotubes."
reach
"Inhibition of mTOR, but not p44/42 MAPK, during nicotine exposure prevented IRS-1 ser636 phosphorylation and normalized insulin sensitivity."
sparser
"IRS-1 is phosphorylated at S636 by mTOR ( xref )."
reach
"The mTOR complex (C) 1/S6K1 blocker rapamycin inhibited the phosphorylation of IRS-1 at Ser636 in cells overexpressing alpha-Syn, suggesting that mTORC1 and S6K1 activation by alpha-Syn causes feedback inhibition of insulin signaling via suppression of IRS-1 function."
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"
reach
"mTOR induced the serine phosphorylation of IRS-1 (Ser 636/639), and such phosphorylation was inhibited by rapamycin."
reach
"At the molecular level, Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of IRS-1 and regulates the phosphorylation of IRS-1 at Ser 636/639 by mTOR."
MTOR phosphorylates IRS1 on S639. 6 / 6
1 | 2 3
reach
"At the molecular level, Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of IRS-1 and regulates the phosphorylation of IRS-1 at Ser 636/639 by mTOR."
rlimsp
"Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR."
reach
"mTOR induced the serine phosphorylation of IRS-1 (Ser 636/639), and such phosphorylation was inhibited by rapamycin."
rlimsp
"Hepatocytes cultured with palmitate displayed hyperphosphorylation of IRS-1 at Ser residues 632/635, known to be phosphorylated by mTOR."
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"
reach
"Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser 636/639 by mTOR."
MTOR phosphorylates IRS1 on S312. 4 / 4
1 | 1 2
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"
sparser
"The latter mechanism is responsible for the described feedback loop inhibition of Akt phosphorylation mediated by mTOR-dependent phosphorylation of IRS-1 at Ser312, the immediate downstream effector protein of the insulin-like growth factor-1 receptor (IGF-1R) [ xref , xref ]."
reach
"Phosphorylation of IRS-1 (Ser312) by P-mTOR promotes conformational changes and subsequent detachment from the receptor and degradation [XREF_BIBR], and inhibits potentiation of Akt by IGF-1R and IRS-1 signaling [XREF_BIBR]."
reach
"The latter mechanism is responsible for the described feedback loop inhibition of Akt phosphorylation mediated by mTOR dependent phosphorylation of IRS-1 at Ser312, the immediate downstream effector protein of the insulin like growth factor-1 receptor (IGF-1R) [XREF_BIBR, XREF_BIBR]."
MTOR phosphorylates IRS1 on S616. 2 / 2
1 | 1
reach
"In addition, activation of the PI3K pathway results in feedback down-regulation of pathway signaling, mediated by an mTOR and S6K phosphorylation and inhibition of IRS-1 at Ser612 XREF_BIBR, XREF_BIBR, XREF_BIBR."
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"
Kinase-active MTOR leads to the phosphorylation of IRS1 on serine. 2 / 2
2 |
bel
"The sentence from Jubilant TNF-alpha activates mTOR which in turn inhibits insulin stimulated tyrosine phosphorylation of IRS1. mTOR phosphorylates IRS1 at Serine residues."
bel
"Here, we demonstrate that nutrients suppress phosphatidylinositol 3 (PI3)-kinase/Akt signaling via Raptor-dependent mTOR (mammalian target of rapamycin)-mediated phosphorylation of insulin receptor substrate 1 (IRS-1). Raptor directly binds to and serves as a scaffold for mTOR-mediated phosphorylation of IRS-1 on Ser636/639"
MTOR leads to the phosphorylation of IRS1 on tyrosine. 2 / 2
| 1 1
reach
"However, the inhibition of mTOR activity by rapamycin (inhibitor of several intracellular pathways including S6K1 pathways) reversed the ER stress reduced tyrosine phosphorylation of IRS-1 and glucose uptake."
rlimsp
"Taken together, these data indicate that FRAP, but not p70(s6k), is a likely physiologic IRS-1 serine kinase that negatively regulates JAK1-dependent IRS-1 tyrosine phosphorylation and suggests that FRAP may modulate IRS-dependent cytokine signaling."
MTOR leads to the phosphorylation of IRS1 on threonine. 1 / 1
| 1
reach
"Overfeeding and metabolic stresses, including high levels of free fatty acids or inflammatory cytokines, enable activation of a number of endogenous protein kinases, such as mTOR, JNK, and IKKbeta, which can phosphorylate IRS1 and IRS2 at serine and threonine residues and which mediate IRS protein ubiquitination and degradation, resulting in insulin resistance [XREF_BIBR]."
MTOR phosphorylates IRS1 on S315. 1 / 1
1 |
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"
MTOR leads to the phosphorylation of IRS1 on S1101. 1 / 1
| 1
reach
"However, Pim1 overexpression did not significantly change the phosphorylation level of ribosomal protein S6 (S240/244), a substrate of activated p70S6K, or phosphorylation of GSK3beta (S9) protein, an AKT substrate, suggesting that the AKT and mTOR signaling pathway did not mediate the phosphorylation of IRS1 on S1101."