Differential modulation of adenylyl cyclases I and II by various Gβ subunits

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 G 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). 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.