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

J. L. Benovic, J. W. Regan, H. Matsui, F. Mayor, S. Cotecchia, L. M.F. Leeb-Lundberg, M. G. Caron, R. J. Lefkowitz

Research output: Contribution to journalArticlepeer-review

112 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)17251-17253
Number of pages3
JournalJournal of Biological Chemistry
Issue number36
StatePublished - 1987

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Agonist-dependent phosphorylation of the α2-adrenergic receptor by the β-adrenergic receptor kinase'. Together they form a unique fingerprint.

Cite this