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Synthetic peptides of the hamster beta 2-adrenoceptor as substrates and inhibitors of the beta-adrenoceptor kinase.

Publication ,  Journal Article
Benovic, JL; Onorato, J; Lohse, MJ; Dohlman, HG; Staniszewski, C; Caron, MG; Lefkowitz, RJ
Published in: Br J Clin Pharmacol
1990

1. The beta-adrenoceptor is one of a number of G protein-coupled receptors which have been proposed to contain seven transmembrane alpha-helices. The function of this receptor appears to be regulated by phosphorylation by a specific enzyme, the beta-adrenoceptor kinase. Synthetic peptides which comprise each of the proposed intra- and extracellular domains of the beta 2-adrenoceptor have been tested as potential substrates and inhibitors of the beta-adrenoceptor kinase. 2. Two peptides which encompass the middle and terminal portions of the carboxyl tail of the receptor served as substrates by beta-adrenoceptor kinase. The kinetics of the phosphorylation reaction, however, suggest that these peptides are 10(6)-fold poorer substrate than the agonist occupied receptor. 3. A number of synthetic peptides also served as inhibitors of beta 2-adrenoceptor phosphorylation by beta-adrenoceptor kinase. In particular, a peptide which comprised the first intracellular loop of the beta 2-adrenoceptor (amino acids 56-74) inhibited most effectively with an IC50 of 40 microM. 4. These results suggest that multiple intracellular regions of the beta-receptor may serve as potential sites of interaction with beta-adrenoceptor kinase. Moreover, these regions may serve as potential targets for the development of specific inhibitors of beta-adrenoceptor kinase which could be used to block homologous desensitization.

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Published In

Br J Clin Pharmacol

DOI

ISSN

0306-5251

Publication Date

1990

Volume

30 Suppl 1

Issue

Suppl 1

Start / End Page

3S / 12S

Location

England

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Substrate Specificity
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Protein Kinase Inhibitors
  • Phosphorylation
  • Pharmacology & Pharmacy
  • Peptides
  • Molecular Sequence Data
  • Kinetics
 

Citation

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Benovic, J. L., Onorato, J., Lohse, M. J., Dohlman, H. G., Staniszewski, C., Caron, M. G., & Lefkowitz, R. J. (1990). Synthetic peptides of the hamster beta 2-adrenoceptor as substrates and inhibitors of the beta-adrenoceptor kinase. Br J Clin Pharmacol, 30 Suppl 1(Suppl 1), 3S-12S. https://doi.org/10.1111/j.1365-2125.1990.tb05462.x
Benovic, J. L., J. Onorato, M. J. Lohse, H. G. Dohlman, C. Staniszewski, M. G. Caron, and R. J. Lefkowitz. “Synthetic peptides of the hamster beta 2-adrenoceptor as substrates and inhibitors of the beta-adrenoceptor kinase.Br J Clin Pharmacol 30 Suppl 1, no. Suppl 1 (1990): 3S-12S. https://doi.org/10.1111/j.1365-2125.1990.tb05462.x.
Benovic JL, Onorato J, Lohse MJ, Dohlman HG, Staniszewski C, Caron MG, et al. Synthetic peptides of the hamster beta 2-adrenoceptor as substrates and inhibitors of the beta-adrenoceptor kinase. Br J Clin Pharmacol. 1990;30 Suppl 1(Suppl 1):3S-12S.
Benovic, J. L., et al. “Synthetic peptides of the hamster beta 2-adrenoceptor as substrates and inhibitors of the beta-adrenoceptor kinase.Br J Clin Pharmacol, vol. 30 Suppl 1, no. Suppl 1, 1990, pp. 3S-12S. Pubmed, doi:10.1111/j.1365-2125.1990.tb05462.x.
Benovic JL, Onorato J, Lohse MJ, Dohlman HG, Staniszewski C, Caron MG, Lefkowitz RJ. Synthetic peptides of the hamster beta 2-adrenoceptor as substrates and inhibitors of the beta-adrenoceptor kinase. Br J Clin Pharmacol. 1990;30 Suppl 1(Suppl 1):3S-12S.
Journal cover image

Published In

Br J Clin Pharmacol

DOI

ISSN

0306-5251

Publication Date

1990

Volume

30 Suppl 1

Issue

Suppl 1

Start / End Page

3S / 12S

Location

England

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Substrate Specificity
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Protein Kinase Inhibitors
  • Phosphorylation
  • Pharmacology & Pharmacy
  • Peptides
  • Molecular Sequence Data
  • Kinetics