Nonphorbol tumor promoters okadaic acid and calyculin-A induce membrane translocation of protein kinase C.
The cell-permeable inhibitors of type 1 and 2A protein phosphatases, okadaic acid and calyculin-A, induced a redistribution of protein kinase C (PKC) activity and immunoreactivity (40 to 60%) from cytosol to membrane in some cell types. Calyculin-A was 100-fold more potent than okadaic acid and required only 5 to 10 nM concentrations to induce this PKC translocation. The concentration of these agents required to induce the redistribution of PKC correlated with the potency of these agents to inhibit both type 1 and 2A protein phosphatases. There was a lag period of 15 to 30 min before the onset of PKC translocation, as this process might have been induced by indirect cellular events triggered by inhibitions of protein phosphatases (1 and 2A). Taken together these results suggest that although the okadaic acid class of tumor promoters and phorbol ester-related agents bind to two different cellular receptors having counteracting enzymic activities, they share a common mechanism of action, namely the induction of cytosol to membrane translocation of PKC.
Gopalakrishna
R
R
Department of Pharmacology and Nutrition, School of Medicine, University of Southern California, Los Angeles 90033.
Chen
Z H
ZH
Gundimeda
U
U
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D015151:Immunoblotting; D007668:Kidney; D007700:Kinetics; D008387:Marine Toxins; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D004988:Ethers, Cyclic; D008387:Marine Toxins; D010080:Oxazoles; D019319:Okadaic Acid; D015240:Phorbol 12,13-Dibutyrate; C059041:calyculin A; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate