Modulation of the substrate specificity of purified human protein kinase C by its activators.

The substrate specificity of purified human protein kinase C was modulated by 12-O-tetradecanoyl-4 beta-phorbol-13-acetate (TPA), dioleoylglycerol, arachidonic acid and lipid A when histone type III-S and myelin basic protein were used as phosphate acceptors. Each activator also showed a distinct pattern in the stimulation of phosphorylation of the kinase itself and of cytosolic placental proteins. The nature of the substrate and the presence of calcium and phospholipid determined the magnitude of the effect observed upon addition of all activators and also the dose dependency of kinase activation by TPA. The apparent Km value for phosphorylation of histone type III-S by the kinase activated by phorbol ester alone and with calcium was 20-30 fold higher than that observed for the enzyme activated by calcium and phospholipid. These observations indicate that the nature and extent of cellular response induced by the activation of C-kinase(s) may be determined by the type of cellular stimulus.