Synergistic action of diacylglycerol and unsaturated fatty acid for protein kinase C activation: its possible implications.
Kinetic properties of the purified alpha, beta, and gamma subspecies of protein kinase C (PKC) to respond to diacylglycerol, phosphatidylserine (PtdSer), and Ca2+ were reinvestigated in the presence of several fatty acids. Although responses of these enzyme subspecies to the lipids slightly differed from one another, the reaction velocity of these subspecies was significantly enhanced by synergistic action of diacylglycerol and a cis-unsaturated fatty acid. Arachidonic, oleic, linoleic, linolenic, and docosahexaenoic acids were active in this role, whereas saturated fatty acids such as palmitic and stearic acids were inactive. Elaidic acid was also inactive. In the presence of both PtdSer and diacylglycerol, the cis-unsaturated fatty acids increased further an apparent affinity of PKC to Ca2+ and allowed the enzyme to exhibit almost full activation at nearly basal levels of Ca2+ concentration. The concentration of fatty acid giving rise to the maximum activation of enzyme was approximately 20-50 microM. The result presented herein implies that the receptor-mediated release of unsaturated fatty acids from phospholipids may take part, in synergy with diacylglycerol, in the activation of PKC even when the Ca2+ concentration is low. A possibility arises, then, that the activation of PKC is an integral part of the signal-induced degradation cascade of various membrane phospholipids, which is initiated by the actions of phospholipase C and phospholipase A2.
Shinomura
T
T
Department of Biochemistry, Kobe University School of Medicine, Japan.
Asaoka
Y
Y
Oka
M
M
Yoshida
K
K
Nishizuka
Y
Y
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D004789:Enzyme Activation; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D007700:Kinetics; D010718:Phosphatidylserines / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D013379:Substrate Specificity
D001095:Arachidonic Acids; D004075:Diglycerides; D005231:Fatty Acids, Unsaturated; D010718:Phosphatidylserines; D016718:Arachidonic Acid; D011493:Protein Kinase C; D002118:Calcium