PHOSPHORYLATION OF MARCKS, NEUROMODULIN, AND NEUROGRANIN BY PROTEIN-KINASE-C EXHIBITS DIFFERENTIAL RESPONSES TO DIACYLGLYCEROLS

Diacylglycerols (DG) derived from brain phosphatidylinositol (PI) and phosphatidylcholine (PC) and synthetic 1,2-dioleoylglycerol (diC(18:1)) and 1,2-dioctanoylglycerol (diC(8)) were tested for their efficacy in stimulating PKC-catalyzed phosphorylation of three physiological substrates in the brain, namely, MARCKS, neuromodulin (Nm), and neurogranin (Ng). The A(0.5) of these DGs for PKC were variable dependent on the protein substrates; the values were lowest with MARCKS and highest with Ng. With Ng as a substrate the A(0.5) of these DGs for PKC gamma were PI- and PC-DGs < diC(18:1) < diC(8). Both PI- and PC-DGs, in spite of their differences in unsaturated fatty acids content, were similarly effective in stimulating PKC. Since the phosphorylation of MARCKS, as compared to those of Nm and Ng, has the lowest A(0.5) With the various DGs, it seems that among these three PKC substrates MARCKS is most readily phosphorylated by PKCs following DG formation in vivo.