Growth factor triggering of protein tyrosine kinase receptors induces signals that cascade to the nucleus, activating mitogenic as well as other responses. Critical components of this process include adapter protein such as Shc, IRS-1 and Gab 1 (GRB-associated binder-1) that lack detectable catalytic activity. These are immediate substrates of receptor tyrosine kinase activity and serve to link activated receptors to downstream signaling components. Whereas Shc has been implicated in signaling by diverse receptor families,IRS-1 serves primarily as the major insulin receptor substrate. Shc and Gab 1 also participate in insulin signaling by linking the insulin receptor to Ras by forming complexes with GRB2 (another adapter protein) and Sos independently of IRS-1. Gab 1 is also thought to be involved in the EGF receptor signaling pathway.