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 PKC beta 1 (dPPA) and PKC alpha, -beta, and -gamma (Tx), but not PKC delta or PKC epsilon 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.
Roivainen
R
R
Department of Neurology, University of California, San Francisco.
Messing
R O
RO
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism*; D016716:PC12 Cells / Q000201:enzymology; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007527:Isoenzymes; D010703:Phorbol Esters; C080287:thymeleatoxin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate