Insulin receptor substrate 1 (UniProt P35568; also known as IRS-1) is encoded by the IRS1 gene (Gene ID 3667) in human. The insulin receptor substrates (IRS-1, IRS-2, IRS-3, and IRS-4) are adaptor proteins involved in modulating cell growth, metabolism, survival, and differentiation by transducing receptor signaling to multiple downstream effectors. IRS family proteins contain a conserved N-terminal pleckstrin homology (PH) domain (a.a. 12-115 of human IRS-1), a phosphotyrosine-binding (PTB) domain (a.a. 160-264 of human IRS-1), and multiple tyrosine phosphorylation sites in the C-terminal region, including Tyr612, Tyr896, Tyr941, Tyr1158, and Tyr1220. The PTB domain meidates the interaction of IRS-1, -2 and -3 with IR juxtamembrane NPXYp motif, facilitating subsequent receptor-mediated IRS tyrosine phosphorylation. Upon phosphorylation, IRS proteins serve as binding sites for Src homology 2 (SH2) domain-containing proteins, such as SHP-2 and PI 3-kinase. Functions of IRS proteins are largely dependent on the phosphorylations of specific tyrosine residues, which in turn are subject to negative regulation by phosphatase activity. In addition, IRS proteins can be phosphorylated by serine/threonine kinases, such as PI-3 kinase, Akt/PKB, GSK-3, mTOR, and PKC, and increased Ser/Thr phosphorylation reduces their binding to IR and tyrosine phosphorylation. Inhibition of PI 3-kinase enhances insulin-stimulated IRS-1 Tyr612/Tyr941 phosphorylation (p85-binding sites) and increases IRS-1 association with PI 3-kinase p85 subunit.
Synonyms: Insulin receptor substrate 1, Tyr941 phosphorylated, IRS-1, Tyr941 phosphorylated
Application: Research CategorySignaling
Other Notes: Concentration: Please refer to lot specific datasheet.