IRS-1 (Insulin receptor substrate-1) is phosphorylated in response to stimulation of cells by insulin. Upon ligand-induced phosphorylation, IRS-1 immediately associates with a series of SH2 domain-containing signaling intermediates such as PI3-kinase, GRB2, Syp and Nck. The level of diversity in structure and function of the SH2-containing proteins which binds activated IRS-1 is important for responsiveness to insulin. IRS phosphorylation elicits the growth and metablic effects of insulin growth factors and insulin by allowing glucose uptake, glycogen synthesis and mitogenic activity. IRS-1 migrates between 170 and 185 kDa and is expressed in most cell types.