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.