Type II adenylylcyclase integrates coincident signals from Gs, Gi, and Gq

Kevin D. Lustig, Bruce R. Conklin, Paul Herzmark, Ronald Taussig, Henry R. Bourne

Research output: Contribution to journalArticlepeer-review

160 Scopus citations


Agonists for Gi-coupled receptors augment Gs-stimulated cAMP synthesis in human embryonic kidney (HEK) 293 cells transiently expressing the type II isozyme of adenylylcyclase (AC-II). This augmentation, mediated by βγ subunits released from activated Gi, can be blocked by expression of the α subunit (γt) of retinal transducin (Gt), which presumably sequesters free βγ (Federman, A. D., Conklin, B. R., Schrader, K. A., Reed, R. R., and Bourne, H. R. (1992) Nature 356, 159-161). The a subunit of Gq, representing a G protein family distinct from both Gs and Gi, mimicked the inhibitory effect of αt, suggesting that hormonal stimulation of endogenous Gq might also release βγ subunits and thereby augment AC-II activity. Agonists for either of two Gq-coupled receptors did augment Gs-stimulated cAMP synthesis in HEK-293 cells expressing AC-II, but this effect was not blocked by expression of αt. The increased stimulation of AC-II was probably not mediated by the release of βγ subunits from Gq 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-II; this increase was synergistic with Gs-mediated activation of AC-II. (b) Treatments that partially inhibit or down-regulate PKC also partially prevented stimulation of AC-II by phorbol esters or by agonists for Gq-coupled receptors. Taken together, these results indicate that AC-II can integrate regulatory signals transmitted by at least three classes of G proteins; extracellular signals acting through Gs are enhanced synergistically by simultaneous signals transduced by Gi or Gq and mediated via βγ or PKC, respectively.

Original languageEnglish (US)
Pages (from-to)13900-13905
Number of pages6
JournalJournal of Biological Chemistry
Issue number19
StatePublished - Jul 5 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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