MOUSE P170 IS A NOVEL PHOSPHATIDYLINOSITOL 3-KINASE CONTAINING A C2 DOMAIN

Phosphatidylinositol (PI) 3-kinases catalyze the formation of 3'-phosp hoinositides, which appear to promote cellular responses to growth fac tors and such membrane trafficking events as insulin-stimulated transl ocation of intracellular glucose transporters. We report here the clon ing of a novel PI 3-kinase, p170, from cDNA of insulin-sensitive mouse 3T3-L1 adipocytes. Mouse p170 utilizes PI and to a limited extent PI 4-P as substrates, in contrast to the PI-specific yeast VPS34 homology PtdIns 3-kinase as the p110 PI 3-kinases, which phosphorylate PI, PI 4-P, and PI 4,5-P-2. Mouse p170 is also distinct from PtdIns 3-kinase of the p110 PI 3-kinases in exhibiting a 10-fold lower sensitivity to wortmannin. Unique structural elements of p170 include C-terminal sequ ences strikingly similar to the phosphoinositide-binding C2 domain of protein kinase C isoforms, synaptotagmins, and other proteins. These f eatures of mouse p170 are shared with a recently cloned Drosophila PI 3-kinase, DmPI3K-68D. Together, these proteins define a new class of P I 3-kinase likely influenced by cellular regulators distinct from thos e acting upon p110- or VPS34-like PI 3-kinases.