ACTIVATION OF PI 3-KINASE BY G-PROTEIN BETA-GAMMA-SUBUNITS

We have reported that fMLP-induced activation of pertussis toxin-sensi tive GTP-binding proteins in THP-1 cells potentiates the insulin-induc ed accumulation of PtdIns(3,4,5)P-3, a product of phosphoinositide 3-k inase (T. Okada et al., Biochem. J. 317, 475-480, 1996). The synergism in PtdIns(3,4,5)P-3 accumulation was observed in Chinese hamster ovar y cells expressing both insulin and fMLP receptors. In rat adipocytes, which represent the physiological target cells of insulin, receptor-m ediated activation of GTP-binding protein by adenosine and prostagland in E-2 potentiated the insulin-induced PtdIns(3,4,5)P-3 accumulation. In cell-free systems, the activity of the p85/p 110 beta subtype of ph osphoinositide 3-kinase was, while that of p85/p 110 alpha was not, st imulated by the beta gamma subunits of the GTP-binding proteins. We pr opose here a hypothesis that the p85/p110 beta subtype is under the co ntrol of both the insulin receptors and the GTP-binding protein-couple d receptors in intact cell systems.