The phorbol derivatives thymeleatoxin and 12-deoxyphorbol-13-O-phenylacetate-10-acetate cause translocation and down-regulation of multiple protein kinase C isozymes

AbstractPhorbol esters such as phorbol 12-myristate,13-acetate (PMA) are potent activators of protein kinase C (PKC), and activate all PKC isozymes except ζ, and λ. Recently, 12-deoxyphorbol-13-O-phenylacetate-20-acetate (dPPA) and thymeleatoxin (Tx) were reported to selectively activate PKCβ1 (dPPA) and PKCα, -β, and -γ (Tx), but not PKCδ or PKCϵ 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 δ and ϵ