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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Benovic, JL; Onorato, J; Lohse, MJ; Dohlman, HG; Staniszewski, C; Caron, MG; Lefkowitz, RJ

Published Date

  • 1990

Published In

Volume / Issue

  • 30 Suppl 1 /

Start / End Page

  • 3S - 12S

PubMed ID

  • 2176526

Pubmed Central ID

  • 2176526

International Standard Serial Number (ISSN)

  • 0306-5251

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2125.1990.tb05462.x

Language

  • eng

Conference Location

  • England