IDENTIFICATION OF A LIGAND-BINDING SITE OF THE HUMAN ENDOTHELIN-A RECEPTOR AND SPECIFIC REGIONS REQUIRED FOR LIGAND SELECTIVITY
被引:27
作者:
ADACHI, M
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h-index: 0
机构:
NIPPON ROCHE RES CTR,DEPT MOLEC GENET,KAMAKURA,KANAGAWA 247,JAPANNIPPON ROCHE RES CTR,DEPT MOLEC GENET,KAMAKURA,KANAGAWA 247,JAPAN
ADACHI, M
[1
]
FURUICHI, Y
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h-index: 0
机构:
NIPPON ROCHE RES CTR,DEPT MOLEC GENET,KAMAKURA,KANAGAWA 247,JAPANNIPPON ROCHE RES CTR,DEPT MOLEC GENET,KAMAKURA,KANAGAWA 247,JAPAN
FURUICHI, Y
[1
]
MIYAMOTO, C
论文数: 0引用数: 0
h-index: 0
机构:
NIPPON ROCHE RES CTR,DEPT MOLEC GENET,KAMAKURA,KANAGAWA 247,JAPANNIPPON ROCHE RES CTR,DEPT MOLEC GENET,KAMAKURA,KANAGAWA 247,JAPAN
MIYAMOTO, C
[1
]
机构:
[1] NIPPON ROCHE RES CTR,DEPT MOLEC GENET,KAMAKURA,KANAGAWA 247,JAPAN
来源:
EUROPEAN JOURNAL OF BIOCHEMISTRY
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1994年
/
220卷
/
01期
关键词:
D O I:
10.1111/j.1432-1033.1994.tb18596.x
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
To investigate the ligand-binding site of the human endothelin-A-receptor subtype (ET(A)), we have produced various chimeric and mutated receptors in chinese hamster ovary cells. The substitution of Lys140 with Ile located in the C-terminus of the second transmembrane region caused a 13-fold reduction in affinity for endothelin-1 (ET-1) and 3.6-fold lower B-max than those values for the original receptor. Correspondingly, the mutated ET(A) receptor with the Lys140-->Ile substitution failed to induce an increase in the intracellular calcium concentration in the presence of 1 nM ET-1. Thus, the Lys140 in the ET(A) receptor is important in ligand binding. ET(A) and ET(B) receptors possess the ET isopeptides selective and non-selective binding activities, respectively Displacement experiments and the binding of I-125-ET-3 to various chimera receptors demonstrated that both the third and fourth extracellular regions, including the flanking transmenbrane regions, are responsible for the ligand-binding selectivity of the ET(A) receptor.