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REPORT

Contents 1 Arrestins as Ligand-Regulated GPCR Scaffolds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Arrestin-Dependent Activation of ERK1/2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Mitogen-Activated Protein Kinases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Binding and Activating the Raf–MEK–ERK Cascade . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Temporal and Spatial Regulation of ERK Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Functionally Distinct ERK Pools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Receptors, GRKs, and Posttranslational Modifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6 Ligand-Dependent Stimulus Trafficking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Arrestin-Dependent Activation of Src Family Kinases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Src Family Nonreceptor Tyrosine Kinases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Binding and Scaffolding of Src Family Kinases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Functions of Arrestin-Bound Src Family Kinases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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E.G. Strungs Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA L.M. Luttrell (*) Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA Research Service of the Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, USA Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 816-CSB, MSC624, Charleston, SC 29425, USA e-mail: [email protected] V.V. Gurevich (ed.), Arrestins - Pharmacology and Therapeutic Potential, Handbook of Experimental Pharmacology 219, DOI 10.1007/978-3-642-41199-1_12, © Springer-Verlag Berlin Heidelberg 2014

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E.G. Strungs and L.M. Luttrell

Abstract The four members of the mammalian arrestin family, two visual and two nonvisual, share the property of stimulus-dependent docking to G protein-coupled receptors. This conformational selectivity permits them to function i

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