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

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Abstract
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-α-phosphatidylinositol 4-monophosphate (PI 4P) and L-α-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 > PI 4P > 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.