INTERFERON-ALPHA ENGAGES THE INSULIN-RECEPTOR SUBSTRATE-1 TO ASSOCIATE WITH THE PHOSPHATIDYLINOSITOL 3'-KINASE

Interferon-alpha (IFN alpha) induces rapid tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), a docking protein with mult iple tyrosine phosphorylation sites that bind to the Src homology 2 (S H2) domains of various signaling proteins. During IFN alpha stimulatio n, the p85 regulatory subunit of the phosphatidylinositol 3'-kinase bi nds via its SH2 domains to tyrosine-phosphorylated IRS-1, and phosphat idylinositol 3'-kinase activity is detected in association with IRS-1. Thus, IFN alpha responses occur by activation of the IRS signaling sy stem, which it shares with insulin, insulin-like growth factor-1, and interleukin-4.