Inhibition of adenylyl cyclase isoforms V and VI by various Gbetagamma subunits
Bayewitch, M.L.; Avidor-Reiss, T.; Levy, R.; Pfeuffer, T.; Nevo, I.; Simonds, W.F.; Vogel, Z.
FASEB Journal 12(11): 1019-1025
1998
ISSN/ISBN: 0892-6638 PMID: 9707174 Document Number: 493174
An intriguing development in the G-protein signaling field has been the finding that not only the Galpha subunit, but also Galpha 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 subunits. Until now,adenylyl cyclase type I has 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 cyclase 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.