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. 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 language | English (US) |
|---|---|
| Pages (from-to) | 17251-17253 |
| Number of pages | 3 |
| Journal | Journal of Biological Chemistry |
| Volume | 262 |
| Issue number | 36 |
| State | Published - 1987 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Biochemistry
Cite this
Agonist-dependent phosphorylation of the α2-adrenergic receptor by the β-adrenergic receptor kinase. / Benovic, J. L.; Regan, John W; Matsui, H.; Mayor, F.; Cotecchia, S.; Leeb-Lundberg, L. M F; Caron, M. G.; Lefkowitz, R. J.
In: Journal of Biological Chemistry, Vol. 262, No. 36, 1987, p. 17251-17253.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Agonist-dependent phosphorylation of the α2-adrenergic receptor by the β-adrenergic receptor kinase
AU - Benovic, J. L.
AU - Regan, John W
AU - Matsui, H.
AU - Mayor, F.
AU - Cotecchia, S.
AU - Leeb-Lundberg, L. M F
AU - Caron, M. G.
AU - Lefkowitz, R. J.
PY - 1987
Y1 - 1987
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0023610955&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023610955&partnerID=8YFLogxK
M3 - Article
VL - 262
SP - 17251
EP - 17253
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 36
ER -