Visualizing signal transduction: Receptors, G-proteins, and adenylate cyclases

Carmen W. Dessauer, Bruce A. Posner, Alfred G. Gilman

Research output: Contribution to journalReview article

44 Scopus citations

Abstract

1. The first glimpses of heterotrimeric G-proteins came with the discoveries of the ubiquitous adenylate cyclase activator, G(s), and the specialized retinal cGMP phosphodiesterase activator, G(t) or transducin. The model that evolved for regulation of adenylate cyclase activity by G-proteins soon proved to be a general paradigm for a large number of signalling pathways. Although many different G-proteins interact with a diverse array of receptors and effectors, each is composed of a guaninenucleotide-binding α-subunit and a tightly associated complex of a β- and a γ-subunit. 2. Receptors catalyse the activation of G-proteins by promoting exchange of GDP for GTP, while G-proteins catalyse their own deactivation as a result of their intrinsic GTPase activity. Crystallographic analysis has described several of the various conformational states that G-proteins undergo as they are activated and deactivated and has provided great insight into the kinetic models of G-protein-mediated signal transduction. 3. The regulation of adenylate cyclase has proven to be intriguing and complex, G(sα) activates all forms of mammalian adenylate cyclase; other G-proteins (G(i), G(o) and G(z)) inhibit certain isoforms of the enzyme. The discovery of new isoforms of adenylate cyclase has revealed synergistic and conditional mechanisms of regulation. These include activation or inhibition by the G-protein βγ-subunit complex, activation by Ca2+-calmodulin, and phosphorylation by protein kinases. The large number of receptors, G-proteins and adenylate cyclases provides a complex signalling network that integrates and interprets a multitude of convergent inputs.

Original languageEnglish (US)
Pages (from-to)527-537
Number of pages11
JournalClinical science
Volume91
Issue number5
DOIs
StatePublished - Jan 1 1996

Keywords

  • Adenylate cyclase
  • Cyclic AMP
  • G-proteins
  • Signal transduction

ASJC Scopus subject areas

  • Medicine(all)

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