Bayewitch M L, Avidor-Reiss T, Levy R, Pfeuffer T, Nevo I, Simonds W F, Vogel Z
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
J Biol Chem. 1998 Jan 23;273(4):2273-6. doi: 10.1074/jbc.273.4.2273.
The accepted dogma concerning the regulation of adenylyl cyclase (AC) activity by G beta gamma dimers states that the various isoforms of AC respond differently to the presence of free G beta gamma. It has been demonstrated that AC I activity is inhibited and AC II activity is stimulated by G beta gamma subunits. This result does not address the possible differences in modulation that may exist among the different G beta gamma heterodimers. Six isoforms of G beta and 12 isoforms of G gamma have been cloned to date. We have established a cell transfection system in which G beta and G gamma cDNAs were cotransfected with either AC isoform I or II and the activity of these isoforms was determined. We found that while AC I activity was inhibited by both G beta 1/gamma 2 and G beta 5/gamma 2 combinations, AC II responded differentially and was stimulated by G beta 1/gamma 2 and inhibited by G beta 5/gamma 2. This finding demonstrates differential modulatory activity by different combinations of G beta gamma on the same AC isoform and demonstrates another level of complexity within the AC signaling system.
关于Gβγ二聚体对腺苷酸环化酶（AC）活性的调节，公认的教条是，AC的各种同工型对游离Gβγ的存在反应不同。已经证明，Gβγ亚基会抑制AC I活性并刺激AC II活性。这一结果并未涉及不同Gβγ异二聚体之间可能存在的调节差异。迄今为止，已克隆出6种Gβ同工型和12种Gγ同工型。我们建立了一种细胞转染系统，其中将Gβ和Gγ cDNA与AC同工型I或II共转染，并测定这些同工型的活性。我们发现，虽然AC I活性受到Gβ1/γ2和Gβ5/γ2组合的抑制，但AC II的反应有所不同，受到Gβ1/γ2的刺激并被Gβ5/γ2抑制。这一发现证明了不同Gβγ组合对同一AC同工型具有不同的调节活性，并证明了AC信号系统内的另一个复杂层面。
