Modulation by palmitoylcarnitine of protein kinase C activation.
Palmitoylcarnitine, a reported protein kinase C inhibitor, enhanced the phorbol ester dependency of the enzyme, augmenting protein kinase C activity in the presence of phorbol esters such as phorbol 12,13-dibutyrate while inhibiting the basal activity measured in the presence of calcium plus phosphatidylserine. Weakly potent phorbol esters such as phorbol 12,13-diacetate and 4-O-methylphorbol 12-myristate 13-acetate were full agonists like phorbol 12,13-dibutyrate for activation of protein kinase C in the presence of palmitoylcarnitine. On the other hand, 1,2-diacylglycerols such as 1,2-diolein were only partially stimulatory. Palmitoylcarnitine did not interfere with the association of protein kinase C with phosphatidylserine, suggesting that its action was on protein kinase C activation per se rather than on priming. A long fatty acid ester, quaternary amine, and anionic charge were needed for the palmitoylcarnitine-like action. Phosphatidylcholine, which possesses these features, partially mimicked the action of palmitoylcarnitine. Palmitoylcarnitine thus appears to be a lipophilic modulator of protein kinase C rather than a simple inhibitor. The results raise the possibility that differences in response between phorbol esters and diacylglycerols may reflect differential ability to activate protein kinase C in the appropriate lipid environment rather than the existence of unique targets for one or the other compound.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives*; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D051379:Mice; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*
D004075:Diglycerides; D006657:Histones; D010703:Phorbol Esters; D010743:Phospholipids; D010172:Palmitoylcarnitine; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D002331:Carnitine; D002118:Calcium; C013965:diolein