Protein kinase C negatively modulated by phorbol ester.
Pretreatment of protein kinase C with 12-O-tetradecanoylphorbol-13-acetate (TPA) and phospholipid resulted in complete inhibition of ATP/phosphotransferase activity, irreversibly. The inactivation by TPA required the phospholipid, and TPA alone did not cause inactivation. Ca2+ and diacylglycerol mimicked TPA. This action of TPA was not general for all protein kinases as it did not accelerate the inactivation of the catalytic subunit of cAMP-dependent protein kinase by phospholipid. The addition of MgATP to the reaction mixture completely protected protein kinase C from being inactivated by TPA, in the presence of phospholipid. The nucleotide-binding site of the enzyme was probably influenced by the binding of TPA and phospholipid.
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D008099:Liver / Q000201:enzymology; D010704:Phorbols / Q000494:pharmacology*; D010743:Phospholipids / Q000494:pharmacology; D010770:Phosphotransferases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011494:Protein Kinases / Q000378:metabolism; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology
D004075:Diglycerides; D010704:Phorbols; D010743:Phospholipids; D014268:Trifluoperazine; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D002746:Chlorpromazine