PHOSPHATIDYLINOSITOL 3'-KINASE - ONE OF THE EFFECTORS OF RAS

Ras proteins are proto-oncogene products that are critical components of signalling pathways leading from cell surface receptors to control of cellular proliferation, morphology and differentiation. The ability of Ras to activate the MAP kinase pathway through interaction with th e serine/threonine kinase Raf is now well established. However, recent work has shown that Ras can also interact directly with the catalytic subunit of phosphatidylinositol 3' kinase and is involved in control of the lipid kinase in intact cells. A model is presented in which bot h tyrosine phosphoprotein interaction with the regulatory p85 subunit and Ras. GTP interaction with the catalytic p110 subunit is required t o achieve optimal activation of phosphatidylinositol 3' kinase in resp onse to extracellular stimuli. The ability of Ras to regulate phosphat idylinositol 3' kinase may be important both in Ras control of cellula r morphology through the actin cytoskeleton and also in Ras control of DNA synthesis.