Phosphatidylinositol 3′-kinase is associated with a serine kinase that is activated by okadaic acid

Okadaic acid (OA) is a potent inhibitor of PP1 and PP2A serine/threonine phosphatases and an inhibitor of phosphatidylinositol 3'-kinase (PI 3-kinase) recruitment/activation. Here we report that PI 3-kinase associates with a serine kinase activated by OA. Whole cell phosphorylation studies showed that PI 3-kinase associates with a wortmannin insensitive 76 kDa serine phosphoprotein (pp76) distinct from the p85 subunit of PI 3-kinase. Serine kinase assays demonstrated that pp76 phosphorylation was dependent upon a wortmannin insensitive serine kinase contained within PI 3-kinase/pp76 complexes and that this kinase had different cation requirements than PI 3-kinase serine kinase. Treatment of whole cells with OA lead to a wortmannin-independent 7.6-fold increase in pp76 serine phosphorylation and to a 7-fold rise in pp76 kinase activity. Together, these findings indicate that pp76 is a PI 3-kinase associated phosphoprotein and suggest that pp76 may be a novel PI S-kinase associated serine kinase that is activated by OA, (C) 1998 Academic Press.