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 (diC18:1) and 1,2-dioctanoylglycerol (diC8) 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 A0.5 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 A0.5 of these DGs for PKC gamma were PI- and PC-DGs < diC18:1 < diC8. 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 A0.5 with the various DGs, it seems that among these three PKC substrates MARCKS is most readily phosphorylated by PKCs following DG formation in vivo.
Section of Metabolic Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510, USA.
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D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D019922:GAP-43 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051579:Neurogranin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D002148:Calmodulin-Binding Proteins; D004075:Diglycerides; D019922:GAP-43 Protein; D047908:Intracellular Signaling Peptides and Proteins; C000619712:Marcks protein, rat; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C496651:Nrgn protein, rat; D010750:Phosphoproteins; D011506:Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D051579:Neurogranin; D011493:Protein Kinase C