GTP-activated GTP binding protein(Gs) in membranes achieved by hormone plus GDP does not serve as a substrate for ADP-ribosylation by cholera toxin.
Adenylate cyclase in the presence of GTP became active by the addition of cholera toxin irrespective of the presence of glucagon, and under the same condition the Gs of these activated enzymes were good acceptor of an ADP-ribose moiety. On the other hand, the cyclase in the presence of GDP remained inactive with cholera toxin but became active by the further addition of glucagon. However, neither of these Gs served as a cholera toxin substrate. Glucagon reduced an inhibitory action of added GDP for cholera toxin plus GTP-stimulated adenylate cyclase activity but did not for toxin plus GTP-enhanced ADP-ribosylation of Gs. These results demonstrate that Gs-GTP complex formation alone is not sufficient for Gs to serve as a cholera toxin substrate, and suggest an additional GTP binding site responsible for ADP-ribosylation by the toxin. Hormone dependent preferential interaction between the GTP binding site on Gs coupled with adenylate cyclase regulation and membrane-associated nucleoside diphosphate kinase is discussed.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002772:Cholera Toxin / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D006150:Guanine Nucleotides / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D008970:Molecular Weight; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D018027:Receptors, Glucagon
D006150:Guanine Nucleotides; D009702:Nucleoside Diphosphate Sugars; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D006153:Guanosine Diphosphate; D000246:Adenosine Diphosphate Ribose; D006160:Guanosine Triphosphate; D005934:Glucagon; D002772:Cholera Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases