Role of PI 3-kinase and SH-PTP2 in insulin action

Insulin bonding to the alpha subunit of its receptor activates the tyrosine kinase of the beta subunit. This induces the tyrosine-phosphorylation of insulin receptor substrates-1 (IRS-1) and a complex formation between IRS-1 and other proteins including GRB2, SH-PTP2, Nck, and phosphoinositide (PI) 3-kinase consisting of a regulatory 85-kDa subunit and a catalytic 110-kDa subunit. We found that insulin-induced binding of the PI 3-kinase activity to IRS-1 generates the signal to activate glucose transport and membrane ruffling. In contrast, insulin-induced binding of SH-PTP2 to IRS-1 generates the signal to activate the Ras protein.