Protein kinase C in cell signaling: strategies for the development of selective inhibitors

Protein kinase C plays a central role in the cellular signaling pathway for the lipophilic second messenger sn-1,2-diacylglycerol, which is involved in many biological responses, including tumor promotion and inflammation. A major effort has been directed at understanding diversity within this system in order to develop strategies for selective inhibition. Two classes of ligands for the regulatory domain of protein kinase C have been identified which, although they function in vitro as activators of the enzyme, paradoxically behave in vivo as partial antagonists. Identification of targets for the phorbol esters distinct from protein kinase C argues that antagonists acting on the regulatory and catalytic domains of protein kinase C will have different spectra of action.