A G-PROTEIN BETA-GAMMA-SUBUNIT-RESPONSIVE PHOSPHOINOSITIDE 3-KINASE ACTIVITY IN HUMAN PLATELET CYTOSOL

Thrombin activates phosphoinositide 3-kinase (PI 3-kinase) in platelet s via a mechanism involving G-proteins, possibly of both the heterotri meric and the low molecular weight families. We have investigated the regulation of PI 3-kinase present in platelet cytosol, and we show tha t this activity can be stimulated by a mixed preparation of G-protein beta gamma-subunits. This stimulation is reversed by preincubation of the beta gamma-subunits with GDP-liganded alpha-subunits. The beta gam ma-stimulated activity is inhibited by wortmannin, a recently identifi ed inhibitor of PI 3-kinase in other systems. In addition, the activit y associates with PDGF receptor phosphotyrosyl peptide and monoclonal antibody designed to interact with the p85 subunit of PI 3-kinase. We suggest that this beta gamma-sensitive activity is related to previous ly identified forms of PI 3-kinase.