Classical and new roles of β-arrestins in the regulation of G-PROTEIN-COUPLED receptors
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- 1 October 2001
- journal article
- review article
- Published by Springer Nature in Nature Reviews Neuroscience
- Vol. 2 (10) , 727-733
- https://doi.org/10.1038/35094577
Abstract
In the classical model of G-protein-coupled receptor (GPCR) regulation, arrestins terminate receptor signalling. After receptor activation, arrestins desensitize phosphorylated GPCRs, blocking further activation and initiating receptor internalization. This function of arrestins is exemplified by studies on the role of arrestins in the development of tolerance to, but not dependence on, morphine. Arrestins also link GPCRs to several signalling pathways, including activation of the non-receptor tyrosine kinase SRC and mitogen-activated protein kinase. In these cascades, arrestins function as adaptors and scaffolds, bringing sequentially acting kinases into proximity with each other and the receptor. The signalling roles of arrestins have been expanded even further with the discovery that the formation of stable receptor-arrestin complexes initiates photoreceptor apoptosis in Drosophila, leading to retinal degeneration. Here we review our current understanding of arrestin function, discussing both its classical and newly discovered roles.Keywords
This publication has 38 references indexed in Scilit:
- Muscarinic Supersensitivity and Impaired Receptor Desensitization in G Protein–Coupled Receptor Kinase 5–Deficient MiceNeuron, 1999
- The GRK4 Subfamily of G Protein-coupled Receptor KinasesJournal of Biological Chemistry, 1999
- Control of Myocardial Contractile Function by the Level of β-Adrenergic Receptor Kinase 1 in Gene-targeted MicePublished by Elsevier ,1998
- G Protein-coupled Receptor Kinase 3 (GRK3) Gene Disruption Leads to Loss of Odorant Receptor DesensitizationJournal of Biological Chemistry, 1997
- β-Arrestin acts as a clathrin adaptor in endocytosis of the β2-adrenergic receptorNature, 1996
- Role of β-Arrestin in Mediating Agonist-Promoted G Protein-Coupled Receptor InternalizationScience, 1996
- The receptor kinase family: primary structure of rhodopsin kinase reveals similarities to the beta-adrenergic receptor kinase.Proceedings of the National Academy of Sciences, 1991
- β-Arrestin: a Protein that Regulates β-adrenergic Receptor FunctionScience, 1990
- Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein).Proceedings of the National Academy of Sciences, 1987
- Rapid affinity purification of retinal arrestin (48 kDa protein) via its light‐dependent binding to phosphorylated rhodopsinFEBS Letters, 1986