TYPE-II ADENYLYLCYCLASE INTEGRATES COINCIDENT SIGNALS FROM GS, GI, AND GQ

Citation
Kd. Lustig et al., TYPE-II ADENYLYLCYCLASE INTEGRATES COINCIDENT SIGNALS FROM GS, GI, AND GQ, The Journal of biological chemistry, 268(19), 1993, pp. 13900-13905
Citations number
52
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
268
Issue
19
Year of publication
1993
Pages
13900 - 13905
Database
ISI
SICI code
0021-9258(1993)268:19<13900:TAICSF>2.0.ZU;2-3
Abstract
Agonists for G(i)-coupled receptors augment G(s)-stimulated cAMP synth esis in human embryonic kidney (HEK) 293 cells transiently expressing the type II isozyme of adenylylcyclase (AC-II). This augmentation, med iated by betagamma subunits released from activated G(i), can be block ed by expression of the alpha subunit (alpha(t)) of retinal transducin (G(t)), which presumably sequesters free betagamma (Federman, A. D., Conklin, B. R., Schrader, K. A., Reed, R. R., and Bourne, H. R. (1992) Nature 356, 159-161). The alpha subunit of G(q), representing a G pro tein family distinct from both G(s) and G(i), mimicked the inhibitory effect of alpha(t), suggesting that hormonal stimulation of endogenous G(q) might also release betagamma subunits and thereby augment AC-II activity. Agonists for either of two G(q)-coupled receptors did augmen t G(s)-stimulated cAMP synthesis in HEK-293 cells expressing AC-II, bu t this effect was not blocked by expression of alpha(t). The increased stimulation of AC-II was probably not mediated by the release of beta gamma subunits from G(q) but rather by activation of protein kinase C (PKC) because of the following. (a) Phorbol esters, which activate PKC directly, elevated cAMP 2-fold in HEK-293 cells transfected with AC-I I; this increase was synergistic with G(s)-mediated activation of AC-I I. (b) Treatments that partially inhibit or down-regulate PKC also par tially prevented stimulation of AC-II by phorbol esters or by agonists for G(q)-coupled receptors. Taken together, these results indicate th at AC-II can integrate regulatory signals transmitted by at least thre e classes of G proteins; extracellular signals acting through G(s) are enhanced synergistically by simultaneous signals transduced by G(i) o r G(q) and mediated via betagamma or PKC, respectively.