Effect of phorbol ester on cyclic adenosine 3':5'-monophosphate-dependent protein kinases in PYS teratocarcinoma-derived cells and counteraction with retinoic acid.
Treatment of PYS cells with the tumor promoter (TPA) has been previously shown to enhance calcium- and phospholipid-dependent protein kinase (PK.C) in the membranes and to decrease its activity in the cytosol. Evidence is presented that 0.1 microM TPA treatment of PYS cells causes an opposite effect on the cyclic AMP-dependent protein kinases (PK.A). Within 10 min TPA led to an increase in PK.A in the cytosol and a concomitant decrease in the membranes, as measured by both the kemptide phosphorylation activity and photoaffinity labeling of RI and RH regulatory subunits of PK.A, with 8-azido-cyclic [32P]AMP. Moreover, the antitumor promoter retinoic acid (RA, 0.1 microM), when added simultaneously with TPA to the PYS cells, completely abolished the TPA effects on PK.A. When RA was added 25 min before TPA, the counteraction was not observed, indicating that RA was counteracting the TPA effect directly. These results suggest that TPA induces a rapid change in the compartmentalization of PK.A between the membrane and the soluble fraction. This possible translocation of PK.A seems to be blocked by RA, suggesting that the early antagonistic effects of RA toward TPA-mediated events occur at the plasma membranes.
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Laboratoire de Physiopathologie du Développement, Paris, France.
Gerbaud
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P
Anderson
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Evain-Brion
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D
D000818:Animals; D001386:Azides / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008970:Molecular Weight; D011494:Protein Kinases / Q000378:metabolism*; D013724:Teratoma / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
D001386:Azides; C017042:8-azidoadenosine-3',5'-monophosphate; D014212:Tretinoin; D000242:Cyclic AMP; D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate