Description
Insulin Receptor Substrate-1 (IRS-1), 165 kDa cytoplasmic docking protein, is one of the major endogenous substrates of the insulin receptor kinase. IRS-1 contains multiple tyrosine phosphorylation motifs that serve as docking sites for SH2 domain containing proteins, which mediate the metabolic and growth promoting functions of insulin. IRS-1 also contains over 30 potential serine/threonine phosphorylation sites. Ser312 of IRS-1 is phosphorylated by JNK and IKK and Ser789 is phosphorylated by SIK-2, a member of AMPK family. The phosphorylation of Tyr612 and Ser636/639 is mediated by the PKC and mTOR pathways, respectively and phosphorylation at Ser1101 is mediated by PKC, resulting in an inhibition of insulin signaling in the cell, suggesting a potential mechanism for insulin resistance in some models of obesity