Protein kinase C activation by phorbol esters: do cysteine-rich regions and pseudosubstrate motifs play a role?

A model for the binding of two activators of protein kinase C (PKC), the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and diacylglycerol, to the enzyme is proposed. It is suggested that each activator is hydrogen-bonded to sulfhydryl groups of cysteine residues and to the carbonyl of an asparagine within the cysteine-rich regions of PKC. This might induce a conformational change that would disrupt the association of the inhibitory pseudosubstrate sequence with the active center of PKC.