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标题：Coupling of the glucagon receptor to adenylyl cyclase by GDP: evidence for two levels of regulation of adenylyl cyclase
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作者：R Iyengar ; L Birnbaumer
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1979
卷号：76
期号：7
页码：3189-3193
DOI：10.1073/pnas.76.7.3189
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In rat liver plasma membranes preactivated with guanosine 5'-[beta,gamma-imido[triphosphate (GuoPP[NH]P), GDP promoted coupling of occupied glucagon receptor to adenylyl cyclase [adenylate cyclase; ATP, pyrophosphate-lyase (cyclizing), EC 4.6.1.1 ] with an apparent association constant Ka of 0.1-0.15 microM. The apparent Ka for the same effect of GTP was 0.2 microM. The effect of GDP was shown not to be due to GTP formed by putative transphosphorylation reaction(s) when ATP was present in the assay as substrate. In membranes not preactivated with GuoPP[NH]P, GDP both competitively inhibited GuoPP[NH]P stimulation of adenylyl cyclase (Ki 0.10 microM) and supported stimulation of cyclizing activity (apparent Ka 0.10 microM) by glucagon. These effects of GDP occurred in the absence of added GTP and in the absence of sufficient formation of GTP by putative transphosphorylation reaction(s) to account for them. It is concluded that two levels of regulation of liver adenylyl cyclase (cyclizing) activity must exit. One level is termed "receptor regulation"; it depends on occupancy of a receptor-related R site by nucleotide and is specific for either GDP or GTP. The second level of regulation is termed "GTPase regulation"; it is inhibited by GDP, depends on both GTP and GTPase, and accounts for activation of cyclizing activity by nonhydrolyzable analogs of GTP. The data suggest that both levels of regulation coexist and may synergize, one mediating responses to stimuli external to the cell (receptor regulation) and the other mediating stimuli of intracellular origin (GTPase regulation).