Phosphoinositide fatty acids regulate phosphatidylinositol 5-kinase, phospholipase C and protein kinase C activities

PtdIns(4,5)P-2 generally results from phosphorylation of PtdIns(4)P by the phosphatidylinositol 5-kinase (PtdIns5-K). Its hydrolysis by phospholipase C (PLC) yields inositol 1,4,5-trisphosphate and diacylglycerol, which stimu lates protein kinase C (PKC). We show that epithelial cells of the cockroac h rectum contain three different inositol lipids: PtdIns(4,5)P-2, PtdIns(4) P, and PtdIns. They are composed of six major fatty acids: palmitic (16:0) stearic (18:0), oleic (18:1n-9), linoleic (18:2n-6), linolenic (18:3n-3), a nd arachidonic (20:4n-6) acids. The fatty acid preference of each of the ab ove enzymes was evaluated by incorporating different fatty acids in pairs i nto membrane lipids. Incorporation of 16:0 plus 18:1n-9 provoked an increas e in PtdIns(4,5)P-2-PLC activity and a decrease in PtdIns5-K activity. In c ontrast, incorporation of 16:0 plus 18:3n-3 led to a potentiation of PtdIns 5-K activity and a decrease in PtdIns(4,5)P-2-PLC activity. Furthermore, PL C and PtdIns5-K acted preferentially on substrates containing 18:3n-3, and 18:3n-3-containing diacylglycerol specifically potentiated PKC activity. Th us, we propose that the fatty acids that make up the phosphoinositides func tion as intracellular modulators of the activity of certain enzymes.