THE PHORBOL DERIVATIVES THYMELEATOXIN AND 12-DEOXYPHORBOL-13-O-PHENYLACETATE-10-ACETATE CAUSE TRANSLOCATION AND DOWN-REGULATION OF MULTIPLE PROTEIN-KINASE-C ISOZYMES

Phorbol esters such as phorbol 12-myristate,13-acetate (PMA) are potent activators of protein kinase C (PKC), and activate all PKC isozymes except zeta and lambda. Recently, 12-deoxyphorbol-13-O-phenylacetate-20-acetate (dPPA) and thymeleatoxin (Tx) were reported to selectively activate PKCbeta1 (dPPA) and PKCalpha, -beta, and -gamma (Tx), but not PKCdelta or PKCepsilon in vitro. We examined the ability of these phorbol derivatives to translocate and down-regulate PKC isozymes in intact cells. Our findings demonstrate that dPPA and Tx cause translocation and down-regulation of multiple PKC isozymes, including delta and epsilon.