Insulin Receptor Substrate (IRS-1) is one of the major substrates of Insulin Receptor Kinase. IRS-1 contains multiple tyrosine phosphorylation motifs that serve as docking sites for SH2 domain-containing proteins (Grb2, p85, SHP-2, Fyn and others) and which mediate the metabolic and growth promoting functions of insulin. IRS-1 also contains over 30 potential Ser/Thr phosphorylation sites for kinases, such as PKA, PKC and MAPK. The phosphorylation of Ser 612 and Ser636/639 are mediated by PKA and mTOR pathways, respectively, resulting in an inhibition of insulin signaling in the cell and suggesting a potential mechanism for insulin resistance in some models of obesity. Once phosphorylated by insulin receptor, IRS-1 recruits the downstream components that mediate the insulin signaling. IRS-1 protein contains a conserved pleckstrin homology (PH) domain located at its amino terminus, adjacent to a phospho-tyrosine binding (PTB) domain.