Gene interactions and pathways from curated databases and text-mining

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IRS1 — MTOR

Pathways - manually collected, often from reviews:

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Hartman et al., Biochem Biophys Res Commun 2001 : Frap dependent serine phosphorylation of IRS-1 inhibits IRS-1 tyrosine phosphorylation
Ozes et al., Proc Natl Acad Sci U S A 2001 (Insulin Resistance) : mTOR induced the serine phosphorylation of IRS-1 ( Ser-636/639 ), and such phosphorylation was inhibited by rapamycin
Zhande et al., Mol Cell Biol 2002 : In contrast, activation of mTOR is not required for IRS-1 degradation in CHO/IR cells
Hartley et al., J Cell Biochem 2002 : We have investigated the role of PI 3-kinase and mTOR in the degradation of IRS-1 induced by insulin ... Inhibition of mTOR with rapamycin resulted in approximately 50 % inhibition of the insulin induced degradation of IRS-1 ... While the role of mTOR in the phosphorylation of IRS-1 appears to proceed primarily through the regulation of PP2A, we also provide evidence that the regulation of p70S6 kinase phosphorylation requires the direct activity of mTOR
Pirola et al., J Biol Chem 2003 (MAP Kinase Signaling System) : PDK1, mTOR , and MAPK inhibitors did not block insulin induced reduction of IRS-1 , suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation
Gual et al., J Biol Chem 2003 (Insulin Resistance) : Furthermore, the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented the osmotic shock induced phosphorylation of IRS-1 on Ser307
Mingo-Sion et al., Breast Cancer Res Treat 2005 (Breast Neoplasms) : PKCdelta and mTOR interact to regulate stress and IGF-I induced IRS-1 Ser312 phosphorylation in breast cancer cells
Shi et al., Mol Cancer Ther 2005 (Multiple Myeloma) : However, by also inhibiting an mTOR dependent serine phosphorylation of insulin receptor substrate-1 (IRS-1) , they may enhance insulin-like growth factor-I (IGF-I) signaling and downstream phosphatidylinositol 3-kinase (PI3K)/AKT activation
Tzatsos et al., Mol Cell Biol 2006 (Diabetes Mellitus, Type 2) : Raptor directly binds to and serves as a scaffold for mTOR mediated phosphorylation of IRS-1 on Ser636/639
O'Reilly et al., Cancer Res 2006 : We now show that mTOR inhibition induces insulin receptor substrate-1 expression and abrogates feedback inhibition of the pathway, resulting in Akt activation both in cancer cell lines and in patient tumors treated with the rapamycin derivative, RAD001
Easton et al., Cancer Cell 2006 : 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
Shah et al., Mol Cell Biol 2006 (Tuberous Sclerosis) : Using two cell culture models of the familial hamartoma syndrome, tuberous sclerosis, we show here that Raptor-mTOR and S6K1 are required for phosphorylation of IRS1 at a subset of serine residues frequently associated with insulin resistance, including S307, S312, S527, S616, and S636 ( of human IRS1 ) ... These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 cell autonomously promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and thus potentially in lesions associated with tuberous sclerosis
Roudier et al., Mol Cancer Ther 2006 (Carcinoma, Hepatocellular...) : Statins also induced mTOR dependent phosphorylation of insulin receptor substrate 1
Krebs et al., Diabetes 2007 : Rapamycin partially inhibited this increase in mTOR mediated S6K phosphorylation and IRS-1 Ser312 and Ser636 phosphorylation
Martin et al., J Biol Chem 2007 (Hyperplasia) : In skeletal muscle and adipocytes, rapamycin relieves mTOR/S6K1 dependent inhibitory phosphorylation of IRS-1 , thus preventing IRS-1 degradation and enhancing PI3K activation
Glynn et al., Appl Physiol Nutr Metab 2008 (Insulin Resistance) : Reduced mTOR/S6K1 signaling during chronic increases in physical activity may play an important regulatory role in the serine phosphorylation of IRS-1 , which should be examined as a potential mechanism for attenuation of insulin resistance associated with increased IRS-1 serine phosphorylation
Mayer et al., Endocrinology 2010 : Thus, a sustained elevation of insulin levels diminishes neuronal insulin signaling through mTOR-S6K1 mediated IRS-1 serine phosphorylation, proteasomal degradation of IRS-1 and lysosomal degradation of the IR
Tiwary et al., Br J Cancer 2011 (Breast Neoplasms) : Importantly, inhibition of MEK and mTOR resulted in increased levels of pAKT and IRS-1 , and a-TEA blocked them
Zhao et al., Am J Physiol Cell Physiol 2011 : Notably, phosphoinositide 3-kinase ( PI 3-kinase ) inhibitor ( PI-103 ) and mammalian target of rapamycin inhibitor ( rapamycin ), which abolished PDGF induced Akt and p70S6kinase phosphorylation, respectively, blocked PDGF induced IRS-1 serine phosphorylation and IRS-2 downregulation
Kim et al., Am J Physiol Endocrinol Metab 2012 : An inhibitor of mTOR , rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 ( Ser ( 636/639 ) ) and blocked the ability of ANG II to impair insulin stimulated phosphorylation of eNOS, nitric oxide production, and mesenteric-arteriole vasodilation
Li et al., Endocrinology 2012 (Insulin Resistance...) : Mammalian target of rapamycin activation caused serine phosphorylation of insulin receptor substrate-1 , which attenuated insulin stimulated tyrosine phosphorylation of insulin receptor substrate-1 and glucose uptake
Geetha et al., J Endocrinol 2012 (Diabetes Mellitus, Type 2...) : These results indicate that PPP1R12A and PP1cd are new members of the insulin stimulated IRS1 signaling complex, and the interaction of PPP1R12A and PP1cd with IRS1 is dependent on Akt and mTOR/raptor activation
Sully et al., Oncogene 2013 (Cell Transformation, Neoplastic) : Rapamycin increases epidermal Akt1 phosphorylation via inhibition of the mTOR complex 1-dependent regulation of insulin receptor substrate-1
Bergman et al., Diabetes 2012 (Insulin Resistance) : Inhibition of mTOR , but not p44/42 MAPK, during nicotine exposure prevented IRS-1 ( ser636 ) phosphorylation and normalized insulin sensitivity
Xu et al., J Biol Chem 2012 : Recent work has implicated a role for cullin-RING E3 ubiquitin ligase 7 ( CRL7 ) in targeting IRS1 for mTORC1/S6K1 dependent degradation
Kim et al., Mol Cell 2012 : Our findings reveal that in addition to persistent mTORC1 signaling, heightened mTORC2 signals can promote insulin resistance due to mTORC2 mediated degradation of IRS-1