IRS1

Insulin receptor substrate 1 ;
IRS-1 ;

disease:Polymorphisms in IRS1 may be involved in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]. ,function:May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit. ,polymorphism:The Arg-971 polymorphism impairs the ability of insulin to stimulate glucose transport , glucose transporter translocation , and glycogen synthesis by affecting the PI3K/AKT1/GSK3 signaling pathway. The polymorphism at Arg-971 may contribute to the in vivo insulin resistance observed in carriers of this variant. Arg-971 could contribute to the risk for atherosclerotic cardiovascular diseases associated with non-insulin-dependent diabetes mellitus (NIDDM) by producing a cluster of insulin resistance-related metabolic abnormalities. In insulin-stimulated human endothelial cells from carriers of the Arg-971 polymorphism , genetic impairment of the IRS1/PI3K/PDPK1/AKT1 insulin signaling cascade results in impaired insulin-stimulated nitric oxide (NO) release and suggested that this may be a mechanism through which the Arg-971 polymorphism contributes to the genetic predisposition to develop endothelial dysfunction and cardiovascular disease. The Arg-971 polymorphism not only reduces phosphorylation of the substrate but allows IRS1 to act as an inhibitor of PI3K , producing global insulin resistance. ,PTM:Phosphorylation of Tyr-896 is required for GRB2-binding. ,PTM:Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor. ,similarity:Contains 1 IRS-type PTB domain. ,similarity:Contains 1 PH domain. ,subunit:Interacts with the NPXY motif of tyrosine-phosphorylated IGF1R and INSR via the PTB domain. Binds to phosphatidylinositol 3-kinase p85 subunit via the phosphorylated YXXM motifs. Binds ROCK1. Binds to UBTF and PIK3CA in nuclear extracts (By similarity) . Interacts with SOCS7. ,

positive regulation of mesenchymal cell proliferation , regulation of glycogen biosynthetic process , regulation of carbohydrate metabolic process , protein complex assembly , cell surface receptor linked signal transduction , enzyme linked receptor protein signaling pathway , transmembrane receptor protein tyrosine kinase signaling pathway ,intracellular signaling cascade , protein kinase cascade , positive regulation of cell proliferation , insulin receptor signaling pathway , response to endogenous stimulus , response to hormone stimulus , positive regulation of biosynthetic process , regulation of catabolic process , positive regulation of catabolic process , positive regulation of signal transduction , negative regulation of signal transduction , response to organic substance , regulation of mesenchymal cell proliferation , positive regulation of macromolecule biosynthetic process , regulation of cellular ketone metabolic process , positive regulation of macromolecule metabolic process , positive regulation of cell communication ,negative regulation of cell communication , regulation of cellular carbohydrate metabolic process , positive regulation of cellular carbohydrate metabolic process , regulation of glucose transport , positive regulation of glucose transport ,regulation of glucose metabolic process , positive regulation of glucose metabolic process , regulation of glucan biosynthetic process , phosphoinositide 3-kinase cascade , regulation of lipid metabolic process , regulation of fatty acid metabolic process , regulation of phosphate metabolic process , regulation of cell migration , positive regulation of cell migration , mammary gland development , positive regulation of cellular biosynthetic process , regulation of cellular catabolic process , positive regulation of cellular catabolic process , regulation of fatty acid beta-oxidation , positive regulation of fatty acid beta-oxidation , response to insulin stimulus , cellular response to insulin stimulus , cellular response to hormone stimulus , regulation of polysaccharide metabolic process , regulation of polysaccharide biosynthetic process , carbohydrate homeostasis , positive regulation of kinase activity , regulation of locomotion ,positive regulation of locomotion , regulation of cell proliferation , regulation of phosphorylation , homeostatic process ,glucose homeostasis , positive regulation of catalytic activity , regulation of carbohydrate biosynthetic process ,response to peptide hormone stimulus , regulation of generation of precursor metabolites and energy , protein kinase B signaling cascade , regulation of kinase activity , regulation of lipid kinase activity , regulation of phosphoinositide 3-kinase activity , positive regulation of phosphoinositide 3-kinase activity , macromolecular complex subunit organization ,positive regulation of molecular function , positive regulation of glycogen biosynthetic process , positive regulation of lipid metabolic process , positive regulation of carbohydrate metabolic process , positive regulation of fatty acid metabolic process , regulation of fatty acid oxidation , positive regulation of fatty acid oxidation , regulation of glucose import , positive regulation of glucose import , regulation of insulin receptor signaling pathway , negative regulation of insulin receptor signaling pathway , positive regulation of insulin receptor signaling pathway , insulin-like growth factor receptor signaling pathway , positive regulation of response to stimulus , negative regulation of response to stimulus ,gland development , chemical homeostasis , regulation of lipid catabolic process , positive regulation of lipid catabolic process , positive regulation of transport , regulation of phosphorus metabolic process , protein oligomerization ,regulation of cell motion , positive regulation of cell motion , protein heterooligomerization , regulation of transferase activity , positive regulation of transferase activity , macromolecular complex assembly , protein complex biogenesis ,