Guanine nucleotide activation and inhibition of adenylate cyclase as modified by islet-activating protein, pertussis toxin, in mouse 3T3 fibroblasts.
Guanine nucleotide regulation of membrane adenylate cyclase activity was uniquely modified after exposure of 3T3 mouse fibroblasts to low concentrations of islet-activating protein (IAP), pertussis toxin. The action of IAP, which occurred after a lag time, was durable and irreversible, and was associated with ADP-ribosylation of a membrane Mr = 41,000 protein. GTP, but not Gpp(NH)p, was more efficient and persistent in activating adenylate cyclase in membranes from IAP-treated cells than membranes from control cells. GTP and Gpp(NH)p caused marked inhibition of adenylate cyclase when the enzyme system was converted to its highly activated state by cholera toxin treatment or fluoride addition, presumably as a result of their interaction with the specific binding protein which is responsible for inhibition of adenylate cyclase. This inhibition was totally abolished by IAP treatment of cells, making it very likely that IAP preferentially modulates GTP inhibitory responses, thereby increasing GTP-dependent activation and negating GTP-mediated inhibition of adenylate cyclase.
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D001886:Bordetella pertussis / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000201:enzymology; D006150:Guanine Nucleotides / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D037342:Pertussis Toxin; D011972:Receptor, Insulin / Q000378:metabolism; D010566:Virulence Factors, Bordetella
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006150:Guanine Nucleotides; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D011972:Receptor, Insulin; D000262:Adenylyl Cyclases; D007545:Isoproterenol