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ID 26023
本文ファイル
著者
Aizaki, Yoshimi
Maruyama, Kei
Nakano-Tetsuka, Mitsue
キーワード
G protein-coupled receptor
DRY motif
Melanin-concentrating hormone
Calcium influx
Site-directed mutagenesis
Constitutive activation
NDC
生物科学・一般生物学
抄録(英)
Rhodopsin family (class A) G protein-coupled receptors possess common key residues or motifs that appear to be important for receptor function. To clarify the roles of the highly conserved amino acid triplet Asp3.49-Arg3.50-Tyr3.51 (DRY motif), we examined how single-substitution mutations of the amino acids in the motif influenced specific features of rat melanin-concentrating hormone receptor 1 (MCH1R) activity. Substitution of either Asp1403.49 or Tyr1423.51 to Ala resulted in nonfunctional receptors, despite the retention of apparent potencies for agonist binding. These loss-of-function phenotypes may be caused by the lack of stimulation for GDP-GTP exchange observed in GTPγS-binding assays. On the other hand, substitution of Arg1413.50 to Ala caused a 4-fold reduction in the agonist binding affinity and, concomitantly, a rightward shift of the dose-dependency curve for calcium mobilization and inhibition of cyclic AMP production. Although many experimental studies have suggested that the DRY motif is involved in maintaining the receptor in its ground state, none of the DRY motif substitutions to Ala in MCH1R led to constitutive activation, in terms of the basal signaling level for ERK1/2 activation or GTPγS binding. These data suggest that the major contribution of the DRY motif in MCH1R is to govern receptor conformation and G protein coupling/recognition.
掲載誌名
Peptides
30巻
5号
開始ページ
974
終了ページ
981
出版年月日
2009-05
出版者
Elsevier Science Inc.
ISSN
0196-9781
NCID
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
Copyright (c) 2009 Elsevier Inc.
関連情報URL
部局名
総合科学研究科