Regulation of protein kinase C activity by cooperative interaction of Zn2+ and Ca2+.
cis-Fatty acids such as oleic acid or linoleic acid have been previously shown to induce full activation of protein kinase C in the absence of Ca2+ and phospholipids (Murakami, K., and Routtenberg, A. (1985) FEBS Lett. 192, 189-193; Murakami, K., Chan, S.Y., and Routtenberg, A. (1986) J. Biol. Chem. 261, 15424-15429). In this study, we have investigated the effects of various metal ions on protein kinase C activity without the interference of Ca2+ since cis-fatty acid requires no Ca2+ for protein kinase C activation. Here we report a specific interaction of Zn2+ with protein kinase C in either a positive or negative cooperative fashion in concert with Ca2+. At low concentrations (approximately 5 microM) of Ca2+, Zn2+ enhances protein kinase C activity induced by both oleic acid and phosphatidylserine/diolein. In contrast, Zn2+ inhibits the activity at higher concentrations (over 50 microM) of Ca2+. In the absence of Ca2+, Zn2+ shows no effect on protein kinase C activity. Our results suggest that Zn2+ does not recognize or interact with protein kinase C in the absence of Ca2+, that protein kinase C possesses high and low affinity Ca2+-binding sites, and that at least one Zn2+-binding site exists which is distinct from Ca2+-binding sites.
Murakami
K
K
Cresap Neuroscience Laboratory, Northwestern University, Evanston, Illinois 60201.
Whiteley
M K
MK
Routtenberg
A
A
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent; D002414:Cations, Monovalent; D007700:Kinetics; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D015032:Zinc / Q000494:pharmacology*
D002413:Cations, Divalent; D002414:Cations, Monovalent; D011493:Protein Kinase C; D015032:Zinc; D002118:Calcium