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Agonist-dependent phosphorylation of the α2-adrenergic receptor by the β-adrenergic receptor kinase

Benovic, J. L. ; Regan, J. W. ; Matsui, H. ; Mayor, F. ; Cotecchia, S. ; Leeb-Lundberg, L. M.F. LU ; Caron, M. G. and Lefkowitz, R. J. (1987) In Journal of Biological Chemistry 262(36). p.17251-17253
Abstract

Desensitization of the β-adrenergic receptor, a receptor which is coupled to the stimulation of adenylate cyclase, may be regulated via phosphorylation by a unique protein kinase. This recently discovered enzyme, known as the β-adrenergic receptor kinase, only phosphorylates the agonist-occupied form of the β-adrenergic receptor. To assess whether receptors coupled to the inhibition of adenylate cyclase might also be substrates, we examined the effects of β-adrenergic receptor kinase on the partially purified human platelet α2-adrenergic receptor. Phosphorylation of the reconstituted α2-adrenergic receptor was dependent on agonist occupancy and was completely blocked by co-incubation with α2-antagonists.... (More)

Desensitization of the β-adrenergic receptor, a receptor which is coupled to the stimulation of adenylate cyclase, may be regulated via phosphorylation by a unique protein kinase. This recently discovered enzyme, known as the β-adrenergic receptor kinase, only phosphorylates the agonist-occupied form of the β-adrenergic receptor. To assess whether receptors coupled to the inhibition of adenylate cyclase might also be substrates, we examined the effects of β-adrenergic receptor kinase on the partially purified human platelet α2-adrenergic receptor. Phosphorylation of the reconstituted α2-adrenergic receptor was dependent on agonist occupancy and was completely blocked by co-incubation with α2-antagonists. The time course of phosphorylation of the α2-adrenergic receptor was virtually identical to that observed with the β-adrenergic receptor with maximum stoichiometries of 7-8 mol of phosphate/mol of receptor in each case. In contrast, the α1-adrenergic receptor, which is coupled to stimulation of phosphatidylinositol hydrolysis, is not a substrate for the β-adrenergic receptor kinase. These results suggest that receptors coupled to either stimulation or inhibition of adenylate cyclase may be regulated by an agonist-dependent phosphorylation mediated by the β-adrenergic receptor kinase.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
262
issue
36
pages
3 pages
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:2826414
  • scopus:0023610955
ISSN
0021-9258
language
English
LU publication?
no
id
bb8b94a7-e6d5-4c82-bfa7-f033b403ba9b
alternative location
http://www.jbc.org/content/262/36/17251.abstract
date added to LUP
2019-06-04 14:20:59
date last changed
2024-01-01 09:17:30
@article{bb8b94a7-e6d5-4c82-bfa7-f033b403ba9b,
  abstract     = {{<p>Desensitization of the β-adrenergic receptor, a receptor which is coupled to the stimulation of adenylate cyclase, may be regulated via phosphorylation by a unique protein kinase. This recently discovered enzyme, known as the β-adrenergic receptor kinase, only phosphorylates the agonist-occupied form of the β-adrenergic receptor. To assess whether receptors coupled to the inhibition of adenylate cyclase might also be substrates, we examined the effects of β-adrenergic receptor kinase on the partially purified human platelet α<sub>2</sub>-adrenergic receptor. Phosphorylation of the reconstituted α<sub>2</sub>-adrenergic receptor was dependent on agonist occupancy and was completely blocked by co-incubation with α<sub>2</sub>-antagonists. The time course of phosphorylation of the α<sub>2</sub>-adrenergic receptor was virtually identical to that observed with the β-adrenergic receptor with maximum stoichiometries of 7-8 mol of phosphate/mol of receptor in each case. In contrast, the α<sub>1</sub>-adrenergic receptor, which is coupled to stimulation of phosphatidylinositol hydrolysis, is not a substrate for the β-adrenergic receptor kinase. These results suggest that receptors coupled to either stimulation or inhibition of adenylate cyclase may be regulated by an agonist-dependent phosphorylation mediated by the β-adrenergic receptor kinase.</p>}},
  author       = {{Benovic, J. L. and Regan, J. W. and Matsui, H. and Mayor, F. and Cotecchia, S. and Leeb-Lundberg, L. M.F. and Caron, M. G. and Lefkowitz, R. J.}},
  issn         = {{0021-9258}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{36}},
  pages        = {{17251--17253}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Biological Chemistry}},
  title        = {{Agonist-dependent phosphorylation of the α<sub>2</sub>-adrenergic receptor by the β-adrenergic receptor kinase}},
  url          = {{http://www.jbc.org/content/262/36/17251.abstract}},
  volume       = {{262}},
  year         = {{1987}},
}