Ser203 as well as Ser204 and Ser207 in fifth transmembrane domain of the human β2-adrenoceptor contributes to agonist binding and receptor activation

Takayuki Sato, Hiroyuki Kobayashi, Taku Nagao, Hitoshi Kurose

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

We examined the contribution of Ser203 of the human β2-adrenoceptor (β2-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 β2-AR and S207A-β2-AR and even lower affinities for S203A-β2-AR and S204A-β2-AR. By contrast, an (-)-isoprenaline derivative with only a para-hydroxyl group showed reduced affinity for wild-type β2-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 β2-AR mutant. These results suggest that Ser203 of the human β2-AR is important for both ligand binding and receptor activation.

Original languageEnglish
Pages (from-to)272-274
Number of pages3
JournalBritish Journal of Pharmacology
Volume128
Issue number2
DOIs
Publication statusPublished - Oct 11 1999
Externally publishedYes

Fingerprint

Adrenergic Receptors
Isoproterenol
Alanine
Hydroxyl Radical
Cyclic AMP
Serine
Ligands
Mutation

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Ser203 as well as Ser204 and Ser207 in fifth transmembrane domain of the human β2-adrenoceptor contributes to agonist binding and receptor activation. / Sato, Takayuki; Kobayashi, Hiroyuki; Nagao, Taku; Kurose, Hitoshi.

In: British Journal of Pharmacology, Vol. 128, No. 2, 11.10.1999, p. 272-274.

Research output: Contribution to journalArticle

@article{7216037ad24e4837be3feb684f92ce5f,
title = "Ser203 as well as Ser204 and Ser207 in fifth transmembrane domain of the human β2-adrenoceptor contributes to agonist binding and receptor activation",
abstract = "We examined the contribution of Ser203 of the human β2-adrenoceptor (β2-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 β2-AR and S207A-β2-AR and even lower affinities for S203A-β2-AR and S204A-β2-AR. By contrast, an (-)-isoprenaline derivative with only a para-hydroxyl group showed reduced affinity for wild-type β2-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 β2-AR mutant. These results suggest that Ser203 of the human β2-AR is important for both ligand binding and receptor activation.",
author = "Takayuki Sato and Hiroyuki Kobayashi and Taku Nagao and Hitoshi Kurose",
year = "1999",
month = "10",
day = "11",
doi = "10.1038/sj.bjp.0702813",
language = "English",
volume = "128",
pages = "272--274",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Ser203 as well as Ser204 and Ser207 in fifth transmembrane domain of the human β2-adrenoceptor contributes to agonist binding and receptor activation

AU - Sato, Takayuki

AU - Kobayashi, Hiroyuki

AU - Nagao, Taku

AU - Kurose, Hitoshi

PY - 1999/10/11

Y1 - 1999/10/11

N2 - We examined the contribution of Ser203 of the human β2-adrenoceptor (β2-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 β2-AR and S207A-β2-AR and even lower affinities for S203A-β2-AR and S204A-β2-AR. By contrast, an (-)-isoprenaline derivative with only a para-hydroxyl group showed reduced affinity for wild-type β2-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 β2-AR mutant. These results suggest that Ser203 of the human β2-AR is important for both ligand binding and receptor activation.

AB - We examined the contribution of Ser203 of the human β2-adrenoceptor (β2-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 β2-AR and S207A-β2-AR and even lower affinities for S203A-β2-AR and S204A-β2-AR. By contrast, an (-)-isoprenaline derivative with only a para-hydroxyl group showed reduced affinity for wild-type β2-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 β2-AR mutant. These results suggest that Ser203 of the human β2-AR is important for both ligand binding and receptor activation.

UR - http://www.scopus.com/inward/record.url?scp=0032586276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032586276&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0702813

DO - 10.1038/sj.bjp.0702813

M3 - Article

C2 - 10510435

AN - SCOPUS:0032586276

VL - 128

SP - 272

EP - 274

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 2

ER -