Schematic illustration of major signaling pathways of insulin action. The phosphorylated insulin receptor binds and phosphorylates IRS proteins and Shc, which bind differentially to various downstream signaling proteins. PI3-kinase is critical for metabolic actions of insulin, such as glucose transport, glycogen synthesis, and protein synthesis, whereas Grb-2/SOS complex, which activates the MAP kinase cascade, is critical in mitogenic response. PI3-kinase probably modulates the mitogenic response as well.