Activation of cellular protein kinase C and mode of inhibitory action of phospholipid-interacting compounds.
12-O-Tetradecanoylphorbol-13-acetate (TPA), that is intercalated into the cell membrane, binds a roughly stoichiometric amount of protein kinase C to produce a catalytically active complex with phospholipid. Local anesthetics and other phospholipid-interacting compounds such as chlorpromazine inhibit profoundly this complex formation in a manner competitive with phospholipid but not with TPA. A tiny change of the membrane phospholipid bilayer structure that is caused by TPA appears to facilitate this unique phospholipid-protein kinase C interaction.
Uratsuji
Y
Y
Nakanishi
H
H
Takeyama
Y
Y
Kishimoto
A
A
Nishizuka
Y
Y
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology; D002852:Chromatography, Ion Exchange; D004789:Enzyme Activation; D017830:Octoxynol; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011092:Polyethylene Glycols; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000779:Anesthetics, Local; D010718:Phosphatidylserines; D010743:Phospholipids; D011092:Polyethylene Glycols; D017830:Octoxynol; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D002746:Chlorpromazine