The activation of protein kinase C by the polyphosphoinositides phosphatidylinositol 4,5-diphosphate and phosphatidylinositol 4-monophosphate.

Protein kinase C(PKC) is a Ca2+- and phospholipid-dependent protein kinase which can be activated by diacylglycerol, a product of polyphosphoinositide hydrolysis. In this report, we show that the polyphosphoinositides L-alpha-phosphatidylinositol 4-monophosphate (PI 4P) and L-alpha-phosphatidylinositol 4,5-diphosphate (PI 4.5DP) can serve as phospholipid cofactors of isolated rat brain PKC. The order of potency of the phosphoinositides in the activation of PKC, PI greater than PI 4P greater than PI 4,5DP, shows a negative correlation with the degree of acidity of the phospholipid head group, whether 1 mM Ca2+ or 200 nM TPA is present in the reaction assay mixture. Although the polyphosphoinositides are by themselves weaker activators of PKC than PI, small amounts of PI 4,5DP cause a two-fold enhancement of PKC in the presence of Ca2+ and PI. While the endogenous phospholipid cofactors of PKC remain to be identified, these results suggest that the small amounts of polyphosphoinositides which are present in cell membranes may play a direct role in the activation of PKC in vivo, by serving as phospholipid cofactors of the enzyme.