Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 1999 Sep;128(2):272-4.
doi: 10.1038/sj.bjp.0702813.

Ser203 as well as Ser204 and Ser207 in fifth transmembrane domain of the human beta2-adrenoceptor contributes to agonist binding and receptor activation

T Sato  1 , H Kobayashi, T Nagao, H Kurose
Affiliations
Comparative Study

Ser203 as well as Ser204 and Ser207 in fifth transmembrane domain of the human beta2-adrenoceptor contributes to agonist binding and receptor activation

T Sato et al. Br J Pharmacol. 1999 Sep.

Erratum in

  • Br J Pharmacol 1999 Dec;128(8):1827

Abstract

We examined the contribution of Ser203 of the human beta2-adrenoceptor (beta2-AR) to the interaction with isoprenaline. The affinity of (-)-isoprenaline was reduced by substitution of an alanine for Ser203, as well as for Ser204 and Ser207. An (-)-isoprenaline derivative with only one hydroxyl group, at the meta-position, showed reduced affinity for wild-type beta2-AR and S207A-beta2-AR and even lower affinities for S203A-beta2-AR and S204A-beta2-AR. By contrast, an (-)-isoprenaline derivative with only a para-hydroxyl group showed reduced affinity for wild-type beta2-AR but the serine to alanine mutations did not cause further decreases. The EC50 value for cyclic AMP generation in response to (-)-isoprenaline was increased, by about 120 fold, for each alanine-substituted beta2-AR mutant. These results suggest that Ser203 of the human beta2-AR is important for both ligand binding and receptor activation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Alignment of the fifth transmembrane domains of various catecholamine receptors.
Figure 2
Figure 2
Effect of mutations of Ser203, Ser204 or Ser207 of human β2-AR on isoprenaline-stimulated cyclic AMP generation. The CHO cells were transfected with the wild-type, S203A-, S204A- or S207A-β2-ARs, labelled with [3H]-adenine, and stimulated with the indicated concentration of (−) - isoprenaline for 10 min in the presence of 1 mM isobutyl-1-methylxanthine. The EC50 values were calculated with the Prism software package. To compare EC50 values between the mutants, the maximal cyclic AMP generation of each experiment was set as 100%, and the other values were normalized to this value.
See this image and copyright information in PMC

References

    1. CAVALLI A., FANELLI F., TADDEI C., DE BENEDETTI P.G., COTECCHIA S. Amino acids of the α1B-adrenergic receptor involved in agonist binding: differences in docking catecholamine to receptor subtypes. FEBS Lett. 1996;399:9–13. - PubMed
    1. COX B.A., HENNINGSEN R.A., SPANOYANNIS A., NEVE R.L., NEVE K.A. Contributions of conserved serine residues to the interactions of ligands with dopamine D2 receptors. J. Neurochem. 1992;59:627–635. - PubMed
    1. DIXON R.A.F., SIGAL I.S., CANDELORE M.R., REGISTER R.B., SCATTERGOOD W., RANDS E., STRADER C.D. Structural features required for ligand binding to the β-adrenergic receptor. EMBO J. 1987;6:3269–3275. - PMC - PubMed
    1. HWA J., PEREZ D.M. The unique nature of the serine interactions for α1-adrenergic receptor agonist binding and activation. J. Biol. Chem. 1996;271:6322–6327. - PubMed
    1. KIKKAWA H., ISOGAYA M., NAGAO T., KUROSE H. The role of the seventh transmembrane region in high affinity binding of a β2-selective agonist TA-2005. Mol. Pharmacol. 1997a;53:128–134. - PubMed

Publication types