Agonist-dependent phosphorylation of the α2-adrenergic receptor by the β-adrenergic receptor kinase
(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
- 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.
- publishing date
- 1987-12-01
- 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}}, }