β-Arrestin Binding to the β2-Adrenergic Receptor Requires Both Receptor Phosphorylation and Receptor Activation*
By C. Krasel, M. Bünemann, K. Lorenz, M. Lohse. Journal of Biological Chemistry, 2005
157 citations recorded by the source corpus.
Homologous desensitization of β2-adrenergic receptors has been shown to be mediated by phosphorylation of the agonist-stimulated receptor by G-protein-coupled receptor kinase 2 (GRK2) followed by binding of β-arrestins to the phosphorylated receptor. Binding of β-arrestin to the receptor is a prerequisite for subsequent receptor desensitization, internalization via clathrin-coated pits, and the initiation of alternative signaling pathways. In this study we have investigated the interactions between receptors and β-arrestin2 in living cells using fluorescence resonance energy transfer. We show that (a) the initial kinetics of β-arrestin2 binding to the receptor is limited by the kinetics of GRK2-mediated receptor phosphorylation; (b) repeated stimulation leads to the accumulation of GRK2-phosphorylated receptor, which can bind β-arrestin2 very rapidly; and (c) the interaction of β-arrestin2 with the receptor depends on the activation of the receptor by agonist because agonist withdrawal leads to swift dissociation of the receptor-β-arrestin2 complex. This fast agonist-controlled association and dissociation of β-arrestins from prephosphorylated receptors should permit rapid control of receptor sensitivity in repeatedly stimulated cells such as neurons.
Subfields: Cellular and Molecular Neuroscience, Computational Theory and Mathematics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/48a9de40df997521988442828e66aa98256381a2
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