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Dual role of the beta(2)-adrenergic receptor C terminus for the binding of beta-arrestin and receptor internalization

Krasel, C., Zabel, U., Lorenz, K., Reiner, S., Al-Sabah, S. and Lohse, M. J. (2008) Dual role of the beta(2)-adrenergic receptor C terminus for the binding of beta-arrestin and receptor internalization. The Journal of Biological Chemistry, 283 (46). pp. 31840-31848. ISSN 1083-351X

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To link to this item DOI: 10.1074/jbc.M806086200

Abstract/Summary

Homologous desensitization of beta(2)-adrenergic and other G-protein-coupled receptors is a two-step process. After phosphorylation of agonist-occupied receptors by G-protein-coupled receptor kinases, they bind beta-arrestins, which triggers desensitization and internalization of the receptors. Because it is not known which regions of the receptor are recognized by beta-arrestins, we have investigated beta-arrestin interaction and internalization of a set of mutants of the human beta(2)-adrenergic receptor. Mutation of the four serine/threonine residues between residues 355 and 364 led to the loss of agonist-induced receptor-beta-arrestin2 interaction as revealed by fluorescence resonance energy transfer (FRET), translocation of beta-arrestin2 to the plasma membrane, and receptor internalization. Mutation of all seven serine/threonine residues distal to residue 381 did not affect agonist-induced receptor internalization and beta-arrestin2 translocation. A beta(2)-adrenergic receptor truncated distal to residue 381 interacted normally with beta-arrestin2, whereas its ability to internalize in an agonist-dependent manner was compromised. A similar impairment of internalization was observed when only the last eight residues of the C terminus were deleted. Our experiments show that the C terminus distal to residue 381 does not affect the initial interaction between receptor and beta-arrestin, but its last eight amino acids facilitate receptor internalization in concert with beta-arrestin2.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy
ID Code:13705
Uncontrolled Keywords:PROTEIN-COUPLED RECEPTORS, BETA-2-ADRENERGIC RECEPTOR, INTRACELLULAR, DOMAINS, ALPHA(2)-ADRENERGIC RECEPTORS, PHOSPHORYLATION SITES, ADRENERGIC-RECEPTOR, OPIOID RECEPTORS, DESENSITIZATION, BETA-ARRESTIN2, SPECIFICITY

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