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Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization.

Publication ,  Journal Article
Bouvier, M; Hausdorff, WP; De Blasi, A; O'Dowd, BF; Kobilka, BK; Caron, MG; Lefkowitz, RJ
Published in: Nature
May 26, 1988

Eukaryotic cells have evolved a variety of mechanisms for dampening their responsiveness to hormonal stimulation in the face of sustained activation. The mechanisms for such processes, collectively referred to as desensitization, often involve alterations in the properties and number of cell-surface hormone receptors. It has been speculated that phosphorylation-dephosphorylation reactions, which are known to regulate the catalytic activities of enzymes, also regulate the function of receptors. Highly specific receptor kinases, such as rhodopsin kinase and beta-adrenergic receptor kinase, which show stimulus-dependent phosphorylation of receptors have been described. Direct evidence for a causal relationship between receptor phosphorylation and desensitization has been lacking however. Here we report that prevention of agonist-stimulated beta 2-adrenergic receptor (beta 2AR) phosphorylation by truncation of its serine and threonine-rich phosphate acceptor segment delays the onset of desensitization. We also show that selective replacement of these serine and threonine residues by alanine and glycine delays desensitization even further. These data provide the first direct evidence that one molecular mechanism of desensitization of G-protein-coupled receptors involves their agonist-induced phosphorylation.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

May 26, 1988

Volume

333

Issue

6171

Start / End Page

370 / 373

Location

England

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Protein Conformation
  • Phosphorylation
  • Mutation
  • Molecular Weight
  • Molecular Sequence Data
  • Kinetics
  • Isoproterenol
  • Humans
  • General Science & Technology
 

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Bouvier, M., Hausdorff, W. P., De Blasi, A., O’Dowd, B. F., Kobilka, B. K., Caron, M. G., & Lefkowitz, R. J. (1988). Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization. Nature, 333(6171), 370–373. https://doi.org/10.1038/333370a0
Bouvier, M., W. P. Hausdorff, A. De Blasi, B. F. O’Dowd, B. K. Kobilka, M. G. Caron, and R. J. Lefkowitz. “Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization.Nature 333, no. 6171 (May 26, 1988): 370–73. https://doi.org/10.1038/333370a0.
Bouvier M, Hausdorff WP, De Blasi A, O’Dowd BF, Kobilka BK, Caron MG, et al. Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization. Nature. 1988 May 26;333(6171):370–3.
Bouvier, M., et al. “Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization.Nature, vol. 333, no. 6171, May 1988, pp. 370–73. Pubmed, doi:10.1038/333370a0.
Bouvier M, Hausdorff WP, De Blasi A, O’Dowd BF, Kobilka BK, Caron MG, Lefkowitz RJ. Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization. Nature. 1988 May 26;333(6171):370–373.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

May 26, 1988

Volume

333

Issue

6171

Start / End Page

370 / 373

Location

England

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Protein Conformation
  • Phosphorylation
  • Mutation
  • Molecular Weight
  • Molecular Sequence Data
  • Kinetics
  • Isoproterenol
  • Humans
  • General Science & Technology