The increase in hormone-stimulated adenylate cyclase activity following Rous sarcoma virus transformation.
Rous sarcoma virus (RSV)-infected chicken embryo cells were used to study the effect of viral transformation on the hormone-stimulated synthesis of cyclic AMP. Transformation by RSV greatly increased the cells' ability to synthesize and accumulate cyclic AMP in response to the beta-adrenergic agonist isoproterenol as compared to untransformed cells. This enhancement was observed in both intact cells and in membranes prepared from these cells. The inclusion of guanosine 5'-0-(3-thiotriphosphate), a nonhydrolyzable analogue of GTP, in assays of adenylate cyclase activity did not abolish the quantitative differences between the transformed and normal cell membranes. Infection of cells by Rous-associated virus, which lacks the oncogene src, did not induce this hyperresponsiveness thus indicating the probable involvement of the src gene product in this phenomenon. The duration of the isoproterenol-induced cyclic AMP elevation was longer in the transformed than in the untransformed cells; transformed cells, unlike untransformed cells, required at least 120 min before full desensitization became established. Membranes prepared from transformed cells specifically bound more than 5 times the quantity of the beta-adrenergic radiolabeled antagonist (-)3H-dihydroalprenolol and 125I-iodocyanopindolol compared to the untransformed cell membranes. Thus, it appears that major differences between the transformed and normal phenotypes reside in the concentration of membrane beta-adrenergic receptors and the inability of RSV-transformed cells to self-limit their response to specific external stimuli.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D002462:Cell Membrane / Q000201:enzymology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002642:Chick Embryo; D015232:Dinoprostone; D004789:Enzyme Activation; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D011458:Prostaglandins E / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000235:genetics
D011458:Prostaglandins E; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D000527:Alprostadil; D015232:Dinoprostone; D007545:Isoproterenol