+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Beta-Adrenergic receptor kinase. Activity of partial agonists for stimulation of adenylate cyclase correlates with ability to promote receptor phosphorylation



Beta-Adrenergic receptor kinase. Activity of partial agonists for stimulation of adenylate cyclase correlates with ability to promote receptor phosphorylation



Journal of Biological Chemistry 263(8): 3893-3897



The beta-adrenergic receptor (beta AR) kinase is a recently discovered enzyme which specifically phosphorylates the agonist-occupied form of the beta-adrenergic receptor. We have utilized the agonist-dependent nature of this phosphorylation reaction to characterize the ability of partial agonists to interact with the receptor. Partial agonists were tested for their ability to: 1) stimulate adenylate cyclase activity in a three-component reconstituted system, and 2) promote phosphorylation of beta AR by beta AR kinase. There is an excellent correlation between the ability of partial agonists to stimulate adenylate cyclase activity and promote receptor phosphorylation by beta AR kinase (y = 1.02x-0.01, r = 0.996, p less than 0.001). Peptide maps of receptor phosphorylated by beta AR kinase in the presence of full or partial agonists are virtually identical with the partial agonist pattern reduced in intensity. Moreover, kinetic studies of beta AR phosphorylation by beta AR kinase suggest that partial agonists alter the Vmax of the reaction with little, if any, effect on the Km. These results suggest that at steady state partial agonists transform a smaller portion of the receptor pool into the conformationally altered or activated form which serves as the substrate for beta AR kinase, although they do not completely rule out the possibility that a partial conformational change is occurring.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 041996210

Download citation: RISBibTeXText

PMID: 2831211


Related references

Desensitization of turkey erythrocyte adenylate cyclase. Beta-adrenergic receptor phosphorylation is correlated with attenuation of adenylate cyclase activity. Journal of Biological Chemistry 259(15): 9742-9749, 1984

Effects of muscarinic cholinergic receptor agonists on beta adrenergic and histamine h 2 receptor stimulated adenylate cyclase activity in guinea pig myo cardium. Clinical Research 30(4): 816A, 1982

Phorbol diesters promote beta-adrenergic receptor phosphorylation and adenylate cyclase desensitization in duck erythrocytes. Biochemical and Biophysical Research Communications 121(3): 973-979, 1984

Agonist regulation of adenylate cyclase activity in neuroblastoma x glioma hybrid NG108-15 cells transfected to co-express adenylate cyclase type II and the beta 2-adrenoceptor. Evidence that adenylate cyclase is the limiting component for receptor-mediated stimulation of adenylate cyclase activity. Biochemical Journal 318: 1033-1039, 1996

Structure-activity relationships of beta-adrenergic receptor-coupled adenylate cyclase: implications of a redox mechanism for the action of agonists at beta-adrenergic receptors. Molecular Pharmacology 31(4): 368-376, 1987

Beta-Adrenergic receptor agonists increase phospholipid methylation, membrane fluidity, and beta-adrenergic receptor-adenylate cyclase coupling. Proceedings of the National Academy of Sciences of the United States of America 76(1): 368-372, 1979

Muscarinic cholinergic receptor modulation of beta adrenergic receptor affinity for catecholamines and catecholamine stimulation of adenylate cyclase activity. Clinical Research 26(3): 486A, 1978

Muscarinic cholinergic agonists increase beta adrenergic receptor affinity for catecholamines and inhibit catecholamine stimulation of adenylate cyclase. Journal of Supramolecular Structure 7(Suppl. 2): 146, 1978

Desensitization of beta-adrenergic receptor-coupled adenylate cyclase activity. Differences following exposure of cells to two full agonists. Biochemical Pharmacology 33(22): 3579-3584, 1984

Beta adrenergic receptor in the brain comparison of tritiated di hydro alprenolol binding sites and a beta adrenergic receptor regulating adenylate cyclase activity in cell free homogenates. Life Sciences 23(16): 1703-1714, 1978

The effect of alpha and beta adrenergic receptor stimulation on the adenylate cyclase activity of human adipocytes. Journal of Cyclic Nucleotide Research 1(5): 321-328, 1975

Partial and full dopamine D1 receptor agonists in mice and rats: relation between behavioural effects and stimulation of adenylate cyclase activity in vitro. European Journal of Pharmacology 213(2): 259-267, 1992

Agonist regulation of adenylate cyclase activity in neuroblastoma glioma hybrid Ng108-15 cells transfected to co-express adenylate cyclase type Ii and the 2 -adrenoceptor. Evidence that adenylate cyclase is the limiting component for receptor-mediated stimulation of adenylate cyclase activity. Biochemical Journal 318(3): 1033-1039, 1996

Carbostyril-based beta-adrenergic agonists: evidence for long lasting or apparent irreversible receptor binding and activation of adenylate cyclase activity in vitro. Naunyn-Schmiedeberg's Archives of Pharmacology 339(1-2): 129-137, 1989

Functional alteration of the beta-adrenergic receptor during desensitization of mammalian adenylate cyclase by beta-agonists. Proceedings of the National Academy of Sciences of the United States of America 81(21): 6686-6690, 1984