Interferon-α engages the insulin receptor substrate-1 to associate with the phosphatidylinositol 3′-kinase

Abstract

Interferon-α (IFNα) induces rapid tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), a docking protein with multiple tyrosine phosphorylation sites that bind to the Src homology 2 (SH2) domains of various signaling proteins. During IFNα stimulation, the p85 regulatory subunit of the phosphatidylinositol 3′-kinase binds via its SH2 domains to tyrosine-phosphorylated IRS-1, and phosphatidylinositol 3′-kinase activity is detected in association with IRS-1. Thus, IFNα responses occur by activation of the IRS signaling system, which it shares with insulin, insulin-like growth factor-1, and interleukin-4.