Inhibition of neuroblastoma cell phosphatidylinositol 3-kinase by CDP-diacylglycerol and phosphatidate.

Phosphatidylinositol (PI) 3-kinase is activated by a variety of agents, including various growth factors, and has been proposed to play a role in initiation of cell growth, proliferation, and differentiation. We here investigate the effect of various membrane lipids on PI 3-kinase immunopurified from human SH-SY5Y neuroblastoma cells. CDP-diacylglycerol (CDP-DAG) inhibited PI 3-kinase activity with an IC50 of 6 microM. Phosphatidate (PA) was also inhibitory (IC50 - 38 microM) as was lysophosphatidate. Neither DAG nor any of the other phospholipids examined affected PI 3-kinase activity. The results offer the possibility that CDP-DAG or PA at critical membrane sites may exert functionally significant metabolic regulation at the point of convergence of the PI 3-kinase-directed and the PI 4-kinase-directed phosphoinositide signal transduction pathways.