Beta-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction.
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.
Biomedical Sciences Division, University of California, Riverside, 1620 Computer Statistics Bldg, Riverside, CA 92521, USA. kathryn.defea@ucr.edu
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D051339:Actin Depolymerizing Factors / Q000502:physiology; D000818:Animals; D019390:Arrestins / Q000737:chemistry / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000071557:beta-Arrestins
D051339:Actin Depolymerizing Factors; D019390:Arrestins; D016328:NF-kappa B; D000071557:beta-Arrestins; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins