The phosphatidylinositol 3-kinase serine kinase phosphorylates IRS-1. Stimulation by insulin and inhibition by Wortmannin.

摘要: Phosphatidylinositol 3-kinase (PI 3-kinase) is a heterodimer composed of an 85-kDa subunit that binds tyrosyl-phosphorylated proteins via its SH2 domains and 110-kDa catalytic subunit. Expression mutagenesis experiments have shown the dual specificity kinase possesses both lipid serine activities. Except for 85- subunits PI 3-kinase, however, no endogenous substrates been identified. The results present study show another target this insulin receptor substrate, IRS-1. Serine phosphorylation IRS-1 as well was demonstrated in immunoprecipitates isolated from rat adipocytes incubated with insulin. In absence insulin, only p85 observed 3-kinase. Both activities were abolished by fungal metabolite Wortmannin. Wortmannin also partially inhibited ability to stimulate glucose transport inhibit lipolysis fat cells. These data raise possibility activity involved signaling. They suggest inhibition or could explain effect diminish action.