Gene interactions and pathways from curated databases and text-mining

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IGF1 — IRS2

Pathways - manually collected, often from reviews:

Text-mined interactions from Literome

Venters et al., Proc Natl Acad Sci U S A 1999 (Nerve Degeneration) : TNF-alpha suppresses IGF-I induced tyrosine phosphorylation of insulin receptor substrate 2 (IRS-2) and inhibits IRS-2-precipitable phosphatidylinositol 3'-kinase activity
Auclair et al., J Clin Endocrinol Metab 1999 (Insulin Resistance) : In contrast, cell resistance to IGF-I occurred at a step distal to IGF-I receptors (IGF-IRs), as AIRs altered neither IGF-I binding nor IGF-I induced IGF-IR autophosphorylation, but inhibited the ability of IGF-IRs to mediate tyrosine phosphorylation of IRS-1 and IRS-2 in response to IGF-I
Ariga et al., Biochem J 2000 : In contrast, cAMP pretreatment potentiated the tyrosine phosphorylation of IRS-2 induced by IGF-I , but did not affect the amount of IRS-2
Richards et al., Endocrinology 2001 : Collectively, these data suggest that the E2-induced decrease in uterine insulin receptor substrate-2 requires IGF-I signaling, is not dependent solely on insulin receptor substrate-1 and PI3K, and is blocked by progesterone as well as by pharmacological inhibition of proteasomal protease activity
Rui et al., J Biol Chem 2001 (Carcinoma, Hepatocellular...) : Regulation of insulin/insulin-like growth factor-1 signaling by proteasome mediated degradation of insulin receptor substrate-2 ... In this study, we show that insulin, IGF-1 , or osmotic stress promoted ubiquitin/proteasome mediated degradation of IRS-2 in 3T3-L1 cells, Fao hepatoma, cells and mouse embryo fibroblasts ; however, insulin/IGF-1 did not promote degradation of IRS-1 in 3T3-L1 preadipocytes or mouse embryo fibroblasts ... In this study, we show that insulin, IGF-1 , or osmotic stress promoted ubiquitin/proteasome mediated degradation of IRS-2 in 3T3-L1 cells, Fao hepatoma, cells and mouse embryo fibroblasts ; however, insulin/IGF-1 did not promote degradation of IRS-1 in 3T3-L1 preadipocytes or mouse embryo fibroblasts ... MG132 or lactacystin, specific inhibitors of 26S proteasome, blocked insulin/IGF-1 induced degradation of IRS-2 and enhanced the detection of ubiquitinated IRS-2
Lingohr et al., Diabetes 2002 (MAP Kinase Signaling System) : It was found that IGF-1 induced phosphatidylinositol 3-kinase (PI3K) association with insulin receptor substrate (IRS)-1 and -2 in a glucose dependent manner, whereas TGF-alpha/EGF did not
Wrede et al., J Mol Endocrinol 2003 : PMA inhibited IGF-I induced activation of PKB, correlating with inhibition of IGF-I induced association of IRS-2 with the p85 regulatory subunit of phosphatidylinositol-3 kinase
Morelli et al., Oncogene 2003 (Breast Neoplasms) : The stabilization of IRS-1 in MDA-MB-231/ER cells was paralleled by the upregulation of the IRS-1/Akt/GSK-3 pathway and improved survival in the presence of IGF-I, whereas IRS-2 was not involved in IGF-I signaling
Lingohr et al., Mol Cell Endocrinol 2003 : However, increased IRS-3 expression blocked glucose/IGF-1 induced IRS-2 translocation from the cytosol to the plasma membrane, dampening IRS-2/IGF-1R interaction and subsequent activation of the PI3K/PKB/GSK3 signaling pathway
Zhang et al., Breast Cancer Res Treat 2004 (Breast Neoplasms) : Immunoprecipitation of IRS substrates followed by anti-phosphotyrosine blotting demonstrated that both IRS-1 and IRS-2 were activated by IGF-I in these cells
Xin et al., Am J Physiol Gastrointest Liver Physiol 2004 (Crohn Disease) : Immunoprecipitation studies demonstrated that IGF-I stimulation resulted in tyrosine phosphorylation of IRS-1, IRS-2 , and Shc
Vincent et al., Neurobiol Dis 2004 : IGF-I : IGF-IR signaling involves phosphorylation of IRS-1 and Shc, but not IRS-2
Briaud et al., J Biol Chem 2005 (Diabetes Mellitus, Type 2) : This glucose/IGF-1 induced decrease in IRS-2 levels was prevented by the proteasomal inhibitor, lactacystin ... In addition, the glucose/IGF-1 induced increase in Ser/Thr phosphorylation of IRS-2 and the subsequent decrease in INS-1 cell IRS-2 protein levels was thwarted by the mammalian target of rapamycin ( mTOR ) inhibitor, rapamycin ... Moreover, adenoviral mediated expression of constitutively active mTOR ( mTORDelta ) further increased glucose/IGF-1 induced Ser/Thr phosphorylation of IRS-2 and decreased IRS-2 protein levels, whereas adenoviral mediated expression of `` kinase-dead '' mTOR ( mTOR-KD ) conversely reduced Ser/Thr phosphorylation of IRS-2 and maintained IRS-2 protein levels
Kim et al., Endocrinology 2005 (Neuroblastoma) : Insulin-like growth factor I induces preferential degradation of insulin receptor substrate-2 through the phosphatidylinositol 3-kinase pathway in human neuroblastoma cells ... In summary, 1 ) IRS-2 is more sensitive to IGF-I mediated degradation ; 2 ) IRS degradation is mediated by phosphatidylinositol 3-kinase and proteasome sensitive pathways ; and 3 ) high levels of IGF-IR , and possibly the subsequent increase in Akt phosphorylation, are required for efficient IRS degradation
Denley et al., Mol Cell Biol 2007 : The specific activation of IRS-2 by IGF-I through the IR does not result in activation of the extracellular signal regulated kinase pathway but does induce delayed low-level activation of the phosphatidylinositol 3-kinase pathway and biological effects such as enhanced cell viability and protection from apoptosis
Barnes et al., Clin Cancer Res 2007 (Head and Neck Neoplasms) : Pretreatment of serum starved 183A or TU159 SCCHN cell lines with A12 ( 10 microg/mL ) blocked IGF stimulated activation of IGF-IR, insulin receptor substrate (IRS)-1 and IRS-2 , mitogen activated protein kinase, and phosphatidylinositol 3-kinase
Heckman et al., Dev Biol 2007 : Because both IGF and p190-B signaling affect IRS-1/2 , we examined IRS-1/2 double knockout embryonic mammary buds
Simmons et al., Am J Physiol Gastrointest Liver Physiol 2007 : In contrast, IGF-I activated both IRS-1 and IRS-2 in intestinal myofibroblasts and IRS-2 activation was upregulated in IRS-1-null myofibroblasts ... In contrast, IGF-I activated both IRS-1 and IRS-2 in intestinal myofibroblasts and IRS-2 activation was upregulated in IRS-1-null myofibroblasts
Hers et al., Blood 2007 : IGF-1 stimulated tyrosine phosphorylation of IRS-1 and IRS-2 and subsequent p85 binding is transient and precedes phosphorylation of protein kinase B (PKB) on Ser473
Nemoto et al., J Pharmacol Sci 2009 : In cultured bovine adrenal chromaffin cells, 1 ) constitutive and negatively regulated activities of GSK-3beta up- and down-regulated insulin receptor, insulin receptor substrate-1 (IRS-1), IRS-2, and Akt levels via controlling proteasomal degradation and protein synthesis ; 2 ) nicotinic receptor/protein kinase C-alpha (PKC-alpha)/extracellular signal regulated kinase ( ERK ) pathway up-regulated IRS-1 and IRS-2 levels, enhancing insulin induced the phosphoinositide 3-kinase (PI3K)/Akt/GSK-3beta pathway ; 3 ) inhibition of calcineurin by cyclosporin A or FK506 down-regulated IRS-2 level, attenuating insulin-like growth factor-I (IGF-I) induced ERK and GSK-3beta pathways ; and 4 ) insulin, IGF-I or therapeutics ( e.g., lithium ) up-regulated the voltage dependent Na(v)1.7 sodium channel
Kwon et al., Cancer Res 2009 (Adenocarcinoma...) : Furthermore, we also showed that insulin receptor substrate (IRS)-2 , but not IRS-1, is involved in regulation of IGF-IR expression, which is most likely not transcriptional control ... Overall, these findings suggest a novel regulatory role of IRS-2 on the expression of IGF-IR through PKCdelta and mTOR in pancreatic cancer cells
de Blaquière et al., Endocr Relat Cancer 2009 (Breast Neoplasms) : We conclude that both IRS-1 and IRS-2 control the migratory response of breast cancer cells to IGF-1 and may, therefore, be key molecules in determining breast cancer spread
Kwon et al., Nutrition 2011 : This improvement was associated with insulin/insulin-like growth factor-1 signaling that was activated by the tyrosine phosphorylation of insulin receptor substrate-2 and serine phosphorylation of Akt, and this in turn increased pancreatic and duodenal homeobox-1 expression
Sadagurski et al., Cell Metab 2012 (Glucose Intolerance...) : Irs2 mediated insulin/IGF1 signaling in the CNS modulates energy balance and glucose homeostasis ; however, the site for Irs2 function is unknown
Fukushima et al., J Biol Chem 2012 : In these cells, IGF-I stimulation induced tyrosine phosphorylation of IGF-IR and IRS-1/2 , but mutated IGF-IR failed to bind PI3K and to induce maximal phosphorylation of GSK3ß and cell proliferation in response to IGF-I
Neukamm et al., PloS one 2012 : IGF-1 stimulation led to increased binding of 14-3-3 to IRS-2 in transfected HEK293 cells and this binding was prevented by inhibition of the PI 3-kinase pathway and an Akt/PKB inhibitor
Haddad et al., J Biol Chem 1997 : Pretreatment of bovine fibroblasts with 10 nM insulin for 48 h blocked subsequent IGF-I stimulated DNA synthesis and the IGF-I induced increase in tyrosyl phosphorylated IRS-2 ... Nonetheless, pretreatment of bovine fibroblasts with IL-4 inhibited IGF-I stimulated DNA synthesis by 50-60 %, concomitant with a decrease in IGF-I induced IRS-2 phosphorylation
Valverde et al., Mol Endocrinol 1998 : Insulin/IGF-I rapidly stimulated IRS-1 and IRS-2 tyrosine phosphorylation, their association with p85alpha, and IRS-1- and IRS-2 associated phosphatidylinositol (PI) 3-kinase activation to the same extent, the effect of insulin being stronger than the effect of IGF-I at the same physiological dose ( 10 nM ) ... Pull-down experiments with glutathione-S-transferase-fusion proteins containing SH2-domains of p85alpha revealed a strong association between IRS-1 and IRS-2 with p85alpha in response to insulin/IGF-I , the insulin effect being stronger than IGF-I
Dews et al., Recept Signal Transduct 1997 : Although the mitogenic function of the IGF-IR may require the activation of insulin receptor substrate-1 (IRS-1) or IRS-2 , an overexpressed IGF-IR is able to protect 32D cells, which lack IRS-1 and IRS-2, from apoptosis caused by Interleukin-3 (IL-3) withdrawal
Kornmann et al., Cancer Res 1998 (Colonic Neoplasms...) : Insulin, IGF-I , and IGF-II enhanced the growth of both cell lines, stimulated tyrosine phosphorylation of IRS-2 , and increased IRS-2 associated phosphatidylinositol (PI) 3-kinase activity
Kim et al., Endocrinology 1998 (Neuroblastoma) : We report here that IGF-I stimulated the tyrosine phosphorylation of the type I IGF receptor ( IGF-IR ) and insulin receptor substrate-2 (IRS-2) in a time- and concentration dependent manner ... Treatment of the cells with PI 3-K inhibitors ( wortmannin and LY294002 ) increased IGF-I induced tyrosine phosphorylation of IRS-2
Horney et al., Am J Physiol 1998 (Diabetic Nephropathies) : MMCs in HG displayed increased IGF-I stimulated insulin receptor substrate-1/2 phosphorylation and activator protein-1 transcriptional activity compared with NG controls
Kim et al., J Biol Chem 1998 (Neuroblastoma) : Insulin receptor substrate 2 and Shc play different roles in insulin-like growth factor I signaling ... In contrast, IGF-I induces a transient tyrosine phosphorylation of IRS-2 and an association of IRS-2 with Grb2 ... In contrast, IGF-I induces a transient tyrosine phosphorylation of IRS-2 and an association of IRS-2 with Grb2