Inhibition of adenylyl cyclase isoforms V and VI by various G^ß subunits

^a Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel
^b Department of Physiological Chemistry II, University of Düsseldorf, Düsseldorf, D-40225 Germany
^c Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, 20892, USA

An intriguing development in the G-protein signaling field has been the finding that not only the G subunit, but also G^ß subunits, affect a number of downstream target molecules. One of the downstream targets of G^ß is adenylyl cyclase, and it has been demonstrated that a number of isoforms of adenylyl cyclase can be either inhibited or stimulated by G^ß subunits. Until now, adenylyl cyclase type I has been the only isoform reported to be inhibited by free G^ß. Here we show by transient cotransfection into COS-7 cells of either adenylyl cyclase V or VI, together with G₂ and various G^ß subunits, that these two adenylyl cyclase isozymes are markedly inhibited by G^ß. In addition, we show that G^ß₁ and G^ß₅ subunits differ in their activity. G^ß₁ transfected alone markedly inhibited adenylyl cylcase V and VI (probably by recruiting endogenous G subunits). On the other hand, G^ß₅ produced less inhibition of these isozymes, and its activity was enhanced by the addition of G₂. These results demonstrate that adenylyl cyclase types V and VI are inhibited by G^ß dimers and that G^ß₁ and G^ß₅ subunits differ in their capacity to regulate these adenylyl cyclase isozymes.—Bayewitch, M. L., Avidor-Reiss, T., Levy, R., Pfeuffer, T., Nevo, I., Simonds, W. F., Vogel, Z. Inhibition of adenylyl cyclase isoforms V and VI by various G^ß subunits. FASEB J. 12, 1019–1025 (1998)

Key Words: G_ß • signal transduction • inhibition • plasmid

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