Direct interaction between membrane-associated nucleoside diphosphate kinase and GTP-binding protein(Gs), and its regulation by hormones and guanine nucleotides.
In previous studies we have proposed that the membrane-associated nucleoside diphosphate kinase (m-NDP kinase) may play a role as a GTP channeling machinery for adenylate cyclase regulation by hormones. In this study, whether the m-NDP kinase has a direct interaction with the component (GTP-binding protein (Gs)) of the glucagon- and beta-adrenergic agonist-sensitive adenylate cyclase systems in rat liver membranes was examined by extraction with octylglucoside, followed by immunoprecipitation by affinity-purified monospecific anti-NDP kinase antibodies. The results demonstrated that the m-NDP kinase and the Gs were extractable as a complexed form and that the complex formation was reversibly regulated, through cell surface receptors, by hormones which had an ability to cause activation of the rat liver adenylate cyclase. Also, it was suggested that guanine nucleotides rather than hormones were primary regulators of the m-NDP kinase-Gs interaction. These results were discussed in relation to the regulatory cycle of the Gs of adenylate cyclase system.
Kimura
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Department of Biochemistry, Tokyo Metropolitan Institute of Gerontology, Japan.
Shimada
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N
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology*; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006153:Guanosine Diphosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007118:Immunoassay; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D009701:Nucleoside-Diphosphate Kinase / Q000302:isolation & purification / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism*; D051381:Rats
D006150:Guanine Nucleotides; D006153:Guanosine Diphosphate; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D005934:Glucagon; D010770:Phosphotransferases; D009701:Nucleoside-Diphosphate Kinase; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol