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Br J Pharmacol. 2008 Mar;153 Suppl 1:S298-309. Epub 2007 Nov 26.

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

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Biomedical Sciences Division, University of California, Riverside, 1620 Computer Statistics Bldg, Riverside, CA 92521, USA.


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, beta-arrestins-1 and 2, independent of heterotrimeric G-protein coupling. This review discusses several known G-protein-independent, beta-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.

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