Phosphatidylcholine-dependent protein kinase C activation. Effects of cis-fatty acid and diacylglycerol on synergism, autophosphorylation and Ca(2+)-dependency.
A long-chain neutral phospholipid, dioleoylphosphatidylcholine, was found to support protein kinase C activation by cis-fatty acid and diacylglycerol (DAG). This effect of phosphatidylcholine (PC) is totally dependent on the presence of cis-fatty acid; PC greatly stimulates the cis-fatty acid-induced protein kinase C activity, but it does not activate protein kinase C at all, even in the presence of DAG, if cis-fatty acid is absent. DAG, however, plays a modulatory role in the presence of Ca2+; it further enhances the PC-potentiated cis-fatty acid activation of protein kinase C. Although the activities of all three protein kinase C subtypes tested (types I, II and III) are supported by this PC mechanism, type III is most sensitive to the DAG effect, and it is activated synergistically by cis-fatty acid and DAG. The potency of PC to support the synergistic activation of this subtype is equivalent to that of phosphatidylserine (PS). There are several differences, however, between PC- and PS-supported synergism observed in type III protein kinase C: (1) Ca(2+)-sensitivity is different; PC requires higher concentrations of Ca2+ (10-20 microM-Ca2+) than those required for PS (micromolar Ca2+); (2) PC/cis-fatty acid/DAG-induced autophosphorylation of protein kinase C subtypes (types I, II and III) is very weak, whereas PS/cis-fatty acid/DAG strongly stimulate autophosphorylation of these subtypes under the conditions at which both PC and PS systems fully activate the protein kinase C in terms of histone phosphorylation. These observations suggest that a neutral phospholipid such as PC may also participate in the activation and differential regulation of protein kinase C.
Chen
S G
SG
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo 14260.
Kulju
D
D
Halt
S
S
Murakami
K
K
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004075:Diglycerides / Q000494:pharmacology*; D004355:Drug Stability; D004357:Drug Synergism; D004789:Enzyme Activation; D005227:Fatty Acids / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012680:Sensitivity and Specificity
D004075:Diglycerides; D005227:Fatty Acids; D007527:Isoenzymes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D011493:Protein Kinase C; C017251:1,2-oleoylphosphatidylcholine; D002118:Calcium