Type II adenylylcyclase integrates coincident signals from G(s), G(i), and G(q)

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

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

Agonists for G(i)-coupled receptors augment G(s)-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 G(i), can be blocked by expression of the α subunit (α(t)) of retinal transducin (G(t)), 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 α subunit of G(q), representing a G protein family distinct from both G(s) and G(i), mimicked the inhibitory effect of α(t), suggesting that hormonal stimulation of endogenous G(q) might also release βγ subunits and thereby augment AC-II activity. Agonists for either of two G(q)-coupled receptors did augment G(s)- stimulated cAMP synthesis in HEK-293 cells expressing AC-II, but this effect was not blocked by expression of α(t). The increased stimulation of AC-II was probably not mediated by the release of βγ 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-II; this increase was synergistic with G(s)- 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 G(q)-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 G(s) are enhanced synergistically by simultaneous signals transduced by G(i) or G(q) and mediated via βγ or PKC, respectively.

Original languageEnglish (US)
Pages (from-to)13900-13905
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number19
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lustig, K. D., Conklin, B. R., Herzmark, P., Taussig, R., & Bourne, H. R. (1993). Type II adenylylcyclase integrates coincident signals from G(s), G(i), and G(q). Journal of Biological Chemistry, 268(19), 13900-13905.