Gene interactions and pathways from curated databases and text-mining

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IRS1 — LEP

Pathways - manually collected, often from reviews:

Text-mined interactions from Literome

Szanto et al., Proc Natl Acad Sci U S A 2000 : In Fao cells, leptin alone had no effects on the insulin signaling pathway, but leptin pretreatment transiently enhanced insulin induced tyrosine phosphorylation and PI 3-kinase binding to IRS-1 , while producing an inhibition of tyrosine phosphorylation and PI 3-kinase binding to IRS-2
Bifulco et al., Placenta 2003 (Choriocarcinoma...) : HG culturing also enhanced leptin stimulated insulin receptor substrate 1 (IRS1) and MAPK phosphorylation
Carvalheira et al., Biol Chem 2003 : This phenomenon parallels the leptin induced tyrosine phosphorylation of STAT3, STAT5b, IRS-1 and IRS-2
Duan et al., J Biol Chem 2004 : SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2 mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin ... Here we report that SH2-B, a JAK2 interacting protein, promotes activation of the PI 3-kinase pathway by recruiting insulin receptor substrate 1 (IRS1) and IRS2 in response to leptin ... Consequently, SH2-B dramatically enhanced leptin stimulated tyrosine phosphorylation of IRS1 and IRS2 in HEK293 cells stably expressing LRb, thus promoting association of IRS1 and IRS2 with the p85 regulatory subunit of PI 3-kinase and phosphorylation and activation of Akt ... SH2-B mutants with lower affinity for IRS1 and IRS2 exhibited reduced ability to promote association of JAK2 with IRS1, tyrosine phosphorylation of IRS1, and association of IRS1 with p85 in response to leptin ... Moreover, deletion of the SH2-B gene impaired leptin stimulated tyrosine phosphorylation of endogenous IRS1 in mouse embryonic fibroblasts (MEF), which was reversed by reintroduction of SH2-B
Benomar et al., Biochem J 2005 : Furthermore, leptin or insulin pre-treatment increased basal PI3K activity and IRS-1 or IRS-2 association with p85 and abolished acute insulin or leptin effect, in addition to the down-regulation of IRS-1 and IRS-2
Hennige et al., FASEB J 2006 (Obesity) : Here we show in various cell models that the adipose hormone leptin , a putative mediator in obesity related insulin resistance, promotes phosphorylation of Ser-318 in Irs1 by a janus kinase 2, Irs2, and PKC dependent pathway
Li et al., Mol Endocrinol 2007 : JAK2 was required for leptin stimulated phosphorylation of insulin receptor substrate 1 (IRS1) , an upstream activator of the phosphatidylinositol 3-kinase pathway
Fang et al., Diabetologia 2009 : Adiponectin can also enhance insulin sensitivity via direct signalling crosstalk ; here we show that enhanced insulin stimulated IRS-1 ( Y612 ) and Akt ( T308 ) phosphorylation in response to fAd was attenuated by leptin
Bełtowski et al., Life Sci 2009 (Disease Models, Animal...) : Leptin increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in the aortic wall, and this effect was impaired in obese and fructose fed animals
Mehebik-Mojaat et al., J Cell Biochem 2009 (Insulin Resistance) : In the presence of leptin and insulin, ( i ) IRS-1 was phosphorylated on Ser ( 307 ) and this effect was prevented by PKA inhibitors, ( ii ) JAK-2 was dephosphorylated, an effect prevented by SHP-1 inhibitor
Moon et al., Diabetologia 2012 : Leptin , but not amylin, increased IRS-1 phosphorylation in GT1-7 hypothalamic, but not in C2C12 muscle and AML12 liver cell lines
Tsuchiya et al., Yakugaku Zasshi 2012 (Disease Progression...) : In in vitro experiments, ATRA significantly enhanced insulin induced IRS1 tyrosine phosphorylation solely in the presence of leptin
Nazarians-Armavil et al., Mol Endocrinol 2013 : Neuronal insulin resistance, as assessed by attenuated Akt phosphorylation, blocked leptin mediated signal transduction and agouti related peptide, urocortin-2, IRS1 , IRS2, and insulin receptor synthesis