Agonist-dependent phosphorylation of the alpha 2-adrenergic receptor by the beta-adrenergic receptor kinase.
Desensitization of the beta-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 beta-adrenergic receptor kinase, only phosphorylates the agonist-occupied form of the beta-adrenergic receptor. To assess whether receptors coupled to the inhibition of adenylate cyclase might also be substrates, we examined the effects of beta-adrenergic receptor kinase on the partially purified human platelet alpha 2-adrenergic receptor. Phosphorylation of the reconstituted alpha 2-adrenergic receptor was dependent on agonist occupancy and was completely blocked by coincubation with alpha 2-antagonists. The time course of phosphorylation of the alpha 2-adrenergic receptor was virtually identical to that observed with the beta-adrenergic receptor with maximum stoichiometries of 7-8 mol of phosphate/mol of receptor in each case. In contrast, the alpha 1-adrenergic receptor, which is coupled to stimulation of phosphatidylinositol hydrolysis, is not a substrate for the beta-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 beta-adrenergic receptor kinase.
Benovic
J L
JL
Department of Medicine (Cardiology), Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
Regan
J W
JW
Matsui
H
H
Mayor
F
F
Cotecchia
S
S
Leeb-Lundberg
L M
LM
Caron
M G
MG
Lefkowitz
R J
RJ
D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D006224:Cricetinae; D010766:Phosphorylation; D010777:Photochemistry; D011494:Protein Kinases / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012243:Rhodopsin / Q000378:metabolism; D013997:Time Factors
D000345:Affinity Labels; D011942:Receptors, Adrenergic, alpha; D012243:Rhodopsin; D011494:Protein Kinases