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lüll Beta-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction Defea KBr J Pharmacol 2008[Mar]; 153 Suppl 1 (Suppl 1): S298-309G-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.|Actin Depolymerizing Factors/physiology[MESH]|Animals[MESH]|Arrestins/chemistry/*physiology[MESH]|Enzyme Activation/physiology[MESH]|GTP-Binding Proteins/chemistry/*physiology[MESH]|Humans[MESH]|Mitogen-Activated Protein Kinases/metabolism[MESH]|NF-kappa B/physiology[MESH]|Phosphatidylinositol 3-Kinases/physiology[MESH]|Signal Transduction/*physiology[MESH]|beta-Arrestins[MESH] |