title: Retinoic acid increases cyclic AMP-dependent protein kinase activity in murine melanoma cells.
abstract: The influence of all trans-retinoic acid on cyclic AMP metabolism was examined in B16-F1 mouse melanoma cells. Treatment of these cells with retinoic acid resulted in a dose-dependent inhibition of cell growth which was accompanied by a concentration-dependent increase in both basal and cyclic AMP-stimulated protein kinase activity, Intracellular levels of cyclic AMP, however, were not altered by retinoid treatment. A protein kinase-deficient variant of B16-F1 (MR-4) did not exhibit decreased growth or increased protein kinase activity in response to retinoic acid treatment. At least 24 h of incubation was required before increased protein kinase activity could be detected in treated B16-F1 cells. Retinoic acid treatment increased the Vmax of protein kinase, but the Ka for cyclic AMP activation was not altered. These findings suggest that in B16 mouse melanoma cells, cyclic AMP-dependent protein kinase may be a target for the growth inhibitory effects of the retinoid.
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation; D008545:Melanoma / Q000201:enzymology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000201:enzymology; D011494:Protein Kinases / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D014212:Tretinoin; D000242:Cyclic AMP; D011494:Protein Kinases