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. 1990;30(Suppl 1):3S–12S. doi: 10.1111/j.1365-2125.1990.tb05462.x

Synthetic peptides of the hamster β2-adrenoceptor as substrates and inhibitors of the β-adrenoceptor kinase

J L Benovic, J Onorato, M J Lohse, H G Dohlman, Claudia Staniszewski, M G Caron, R J Lefkowitz
PMCID: PMC1368092  PMID: 2176526

Abstract

1 The β-adrenoceptor is one of a number of G protein-coupled receptors which have been proposed to contain seven transmembrane α-helices. The function of this receptor appears to be regulated by phosphorylation by a specific enzyme, the β-adrenoceptor kinase. Synthetic peptides which comprise each of the proposed intra- and extracellular domains of the β2-adrenoceptor have been tested as potential substrates and inhibitors of the β-adrenoceptor kinase.

2 Two peptides which encompass the middle and terminal portions of the carboxyl tail of the receptor served as substrates by β-adrenoceptor kinase. The kinetics of the phosphorylation reaction, however, suggest that these peptides are 106-fold poorer substrates than the agonist occupied receptor.

3 A number of synthetic peptides also served as inhibitors of β2-adrenoceptor phosphorylation by β-adrenoceptor kinase. In particular, a peptide which comprised the first intracellular loop of the β2-adrenoceptor (amino acids 56-74) inhibited most effectively with an IC50 of 40 μM.

4 These results suggest that multiple intracellular regions of the β-receptor may serve as potential sites of interaction with β-adrenoceptor kinase. Moreover, these regions may serve as potential targets for the development of specific inhibitors of β-adrenoceptor kinase which could be used to block homologous desensitization.

Keywords: Receptors, desensitization, phosphorylation, kinases, inhibitors

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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