Although most tyrosine kinase growth factor receptors directly bind Src homology 2 (SH2) proteins, the insulin receptor, and a select group of other hormone receptors-including an emerging group of cytokine receptors-phosphorylate intracellular insulin receptor substrate (IRS) proteins, which subsequently bind SH2 proteins. There are currently two members of the IRS family (IRS-i and IRS-2); these IRS proteins contain elements of substantial similarity, but may also play divergent roles in mammalian physiology. The engagement of IRS proteins by other receptors suggests that IRS proteins mediate diverse biological signals.(Trends Endocrinol Metab 1995$ x209-2 1.5).