A primate-dominant third glycosylation site of the beta2-adrenergic receptor routes receptors to degradation during agonist regulation

The Journal of Biological Chemistry
Jeanne Mialet-PerezStephen B Liggett

Abstract

beta(2)-adrenergic receptors (beta(2)AR) of all species are N-linked glycosylated at amino terminus residues approximately 6 and approximately 15. However, the human beta(2)AR has a potential third N-glycosylation site at ECL2 residue 187. To determine whether this residue is glycosylated and to ascertain function, all possible single/multiple Asn --> Gln mutations were made in the human beta(2) AR at positions 6, 15, and 187 and were expressed in Chinese hamster fibroblast cells. Substitution of Asn-187 alone or with Asn-6 or Asn-15 decreased the apparent molecular mass of the receptor on SDS-PAGE in a manner consistent with Asn-187 glycosylation. All receptors bound the agonist isoproterenol and functionally coupled to adenylyl cyclase. However, receptors without 187 glycosylation failed to display long term agonist-promoted down-regulation. In contrast, loss of Asn-6/Asn-15 glycosylation did not alter down-regulation. Cell surface distribution and agonist-promoted internalization of receptors and recruitment of beta-arrestin 2 were unaffected by the loss of 187 glycosylation. Furthermore, acutely internalized wild-type and Gln-187 receptors were both localized by confocal microscopy to early endosomes. During prolonged agoni...Continue Reading

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Citations

Nov 4, 2005·Proceedings of the American Thoracic Society·Dennis W McGraw, Stephen B Liggett
Nov 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Susana GranellGiulia Baldini
Sep 1, 2006·Expert Opinion on Drug Discovery·Peter P Mager, Peter Illes
Sep 21, 2007·Neurochemistry International·Alice C DuttonNicholas M Barnes
May 10, 2008·Journal of Neurochemistry·Claudia ReichlingMaik Behrens
Nov 6, 2007·Biochemical and Biophysical Research Communications·Peng HuangLee-Yuan Liu-Chen
Jul 15, 2005·Cellular Signalling·Matthew T DuvernayGuangyu Wu
May 4, 2005·Molecular and Cellular Endocrinology·Christine L Clouser, K M J Menon
Dec 12, 2017·FEBS Open Bio·Paweł KozielewiczNicholas M Barnes
Oct 20, 2006·Journal of Biochemistry·Shuji Noguchi, Yoshinori Satow
Jun 15, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Alfredo PanebraStephen B Liggett
Jan 24, 2006·Journal of Chemical Information and Modeling·Debra L BautistaTimothy Hammitt

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