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

Publication ,  Journal Article
Benovic, JL; Staniszewski, C; Mayor, F; Caron, MG; Lefkowitz, RJ
Published in: J Biol Chem
March 15, 1988

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.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

March 15, 1988

Volume

263

Issue

8

Start / End Page

3893 / 3897

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Phosphorylation
  • Peptide Mapping
  • Lung
  • Kinetics
  • Enzyme Activation
  • Cyclic AMP-Dependent Protein Kinases
  • Cricetinae
 

Citation

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Benovic, J. L., Staniszewski, C., Mayor, F., Caron, M. G., & Lefkowitz, R. J. (1988). beta-Adrenergic receptor kinase. Activity of partial agonists for stimulation of adenylate cyclase correlates with ability to promote receptor phosphorylation. J Biol Chem, 263(8), 3893–3897.
Benovic, J. L., C. Staniszewski, F. Mayor, M. G. Caron, and R. J. Lefkowitz. “beta-Adrenergic receptor kinase. Activity of partial agonists for stimulation of adenylate cyclase correlates with ability to promote receptor phosphorylation.J Biol Chem 263, no. 8 (March 15, 1988): 3893–97.
Benovic JL, Staniszewski C, Mayor F, Caron MG, Lefkowitz RJ. beta-Adrenergic receptor kinase. Activity of partial agonists for stimulation of adenylate cyclase correlates with ability to promote receptor phosphorylation. J Biol Chem. 1988 Mar 15;263(8):3893–3897.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

March 15, 1988

Volume

263

Issue

8

Start / End Page

3893 / 3897

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Phosphorylation
  • Peptide Mapping
  • Lung
  • Kinetics
  • Enzyme Activation
  • Cyclic AMP-Dependent Protein Kinases
  • Cricetinae