Bayewitch M L, Avidor-Reiss T, Levy R, Pfeuffer T, Nevo I, Simonds W F, Vogel Z
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
FASEB J. 1998 Aug;12(11):1019-25. doi: 10.1096/fasebj.12.11.1019.
An intriguing development in the G-protein signaling field has been the finding that not only the Galpha subunit, but also Gbetagamma subunits, affect a number of downstream target molecules. One of the downstream targets of Gbetagamma is adenylyl cyclase, and it has been demonstrated that a number of isoforms of adenylyl cyclase can be either inhibited or stimulated by Gbetagamma subunits. Until now, adenylyl cyclase type I has been the only isoform reported to be inhibited by free Gbetagamma. Here we show by transient cotransfection into COS-7 cells of either adenylyl cyclase V or VI, together with Ggamma2 and various Gbeta subunits, that these two adenylyl cyclase isozymes are markedly inhibited by Gbetagamma. In addition, we show that Gbeta1 and Gbeta5 subunits differ in their activity. Gbeta1 transfected alone markedly inhibited adenylyl cylcase V and VI (probably by recruiting endogenous Ggamma subunits). On the other hand, Gbeta5 produced less inhibition of these isozymes, and its activity was enhanced by the addition of Ggamma2. These results demonstrate that adenylyl cyclase types V and VI are inhibited by Gbetagamma dimers and that Gbeta1 and Gbeta5 subunits differ in their capacity to regulate these adenylyl cyclase isozymes.
G蛋白信号传导领域一个有趣的进展是，人们发现不仅Gα亚基，而且Gβγ亚基也会影响许多下游靶分子。Gβγ的下游靶标之一是腺苷酸环化酶，并且已经证明，腺苷酸环化酶的许多同工型可以被Gβγ亚基抑制或刺激。到目前为止，I型腺苷酸环化酶是唯一被报道可被游离Gβγ抑制的同工型。在此，我们通过将腺苷酸环化酶V或VI与Gγ2和各种Gβ亚基一起瞬时共转染到COS-7细胞中，表明这两种腺苷酸环化酶同工酶明显受到Gβγ的抑制。此外，我们表明Gβ1和Gβ5亚基在活性上存在差异。单独转染的Gβ1显著抑制腺苷酸环化酶V和VI（可能是通过募集内源性Gγ亚基）。另一方面，Gβ5对这些同工酶的抑制作用较小，并且通过添加Gγ2可增强其活性。这些结果表明，V型和VI型腺苷酸环化酶受到Gβγ二聚体的抑制，并且Gβ1和Gβ5亚基在调节这些腺苷酸环化酶同工酶的能力上存在差异。
