Synergistic activation of type III protein kinase C by cis-fatty acid and diacylglycerol.
Micromolar concentrations of cis-fatty acid synergistically activate type III protein kinase C with diacylglycerol. This synergistic effect occurs at low concentrations of cis-fatty acid and diacylglycerol, and it is capable of inducing almost full activation of this protein kinase C subtype at a physiologically relevant Ca2+ concentration (2 microM). The synergistic activation mode can be observed even in the absence of Ca2+, but micromolar Ca2+ significantly enhances the type III protein kinase C activation. cis-Fatty acid also augments the diacylglycerol-induced activation of other subtypes (type I and II), although the effect is smaller than that observed in type III. Neither the diacylglycerol- nor the cis-fatty acid-dependent mode of activation can fully activate any of these subtypes at a physiological concentration of Ca2+ (2 microM). Our results suggest that the generation of three second messengers, i.e. the increase in intracellular Ca2+ concentration and the generation of both cis-fatty acid and diacylglycerol in the cell, may be necessary signals for protein kinase C activation, particularly for type III protein kinase C.
Chen
S G
SG
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo 14260.
Murakami
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D002845:Chromatography; D002848:Chromatography, DEAE-Cellulose; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D004075:Diglycerides / Q000494:pharmacology*; D004357:Drug Synergism; D017886:Durapatite; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004789:Enzyme Activation; D006882:Hydroxyapatites; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000494:pharmacology; D011493:Protein Kinase C / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats
D004075:Diglycerides; D006882:Hydroxyapatites; D007527:Isoenzymes; D009829:Oleic Acids; D010718:Phosphatidylserines; C044295:1,2-dioctanoylglycerol; D016718:Arachidonic Acid; D019301:Oleic Acid; C042511:1,2-dioleoylphosphatidylserine; D017886:Durapatite; D015118:Eicosapentaenoic Acid; D011493:Protein Kinase C