Insulin Receptor Substrate 1 (IRS 1) is an 165 kDa multi-phosphorylated cytoplasmic docking protein involved in metabolic and proliferative signaling by insulin, IL-4, and other cytokines. IRS 1 functions to enhance growth hormone-induced proliferative signaling. The activated insulin receptor phosphorylates IRS proteins on multiple tyrosine residues that serve as docking sites for downstream mediators of metabolic actions such as phosphatidylinositol-3 kinase. IRS proteins also undergo serine phosphorylation, which regulates its function. Phosphorylation of human IRS 1 at serines 312 and 616 (serines 307 and 612 in mouse) results in the impairment of metabolic insulin signaling pathways.