β-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction

Authors

  • K DeFea

    Corresponding author
    1. Biomedical Sciences Division, University of California, Riverside, CA, USA
      Biomedical Sciences Division, University of California, Riverside, 1620 Computer Statistics Bldg, Riverside, CA 92521, USA. E-mail: kathryn.defea@ucr.edu
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Biomedical Sciences Division, University of California, Riverside, 1620 Computer Statistics Bldg, Riverside, CA 92521, USA. E-mail: kathryn.defea@ucr.edu

Abstract

G-protein-coupled receptors (GPCRs), also known as seven transmembrane receptors (7-TMRs), are the largest protein receptor superfamily in the body. These receptors and their ligands direct a diverse array of physiological responses, and hence have broad relevance to numerous diseases. As a result, they have generated considerable interest in the pharmaceutical industry as drug targets. Recently, GPCRs have been demonstrated to elicit signals through interaction with the scaffolding proteins, β-arrestins-1 and 2, independent of heterotrimeric G-protein coupling. This review discusses several known G-protein-independent, β-arrestin-dependent pathways and their potential physiological and pharmacological significance. The emergence of G-protein-independent signalling changes the way in which GPCR signalling is evaluated, from a cell biological to a pharmaceutical perspective and raises the possibility for the development of pathway specific therapeutics.

British Journal of Pharmacology (2008) 153, S298–S309; doi:10.1038/sj.bjp.0707508; published online 26 November 2007

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