CONSTITUTIVE ACTIVATION OF THE THYROTROPIN RECEPTOR BY DELETION OF A PORTION OF THE EXTRACELLULAR DOMAIN

被引：45

作者：

ZHANG, ML ^{[1
]}

SUGAWA, H ^{[1
]}

KOSUGI, S ^{[1
]}

MORI, T ^{[1
]}

机构：

[1] KYOTO UNIV,SCH MED,DEPT LAB MED,SAKYO KU,KYOTO 60601,JAPAN

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1995年 / 211卷 / 01期

关键词：

D O I：

10.1006/bbrc.1995.1797

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：

Mutations involving the transmembrane domain of the thyrotropin receptor (TSHR) confer constitutive activation of the receptor and can cause human diseases. Naturally occurring activating mutations identified to date are located only in the transmembrane domain of the receptor. We now report a mutant involving the extracellular domain of the TSHR which also shows constitutive activation. This mutation is missing residues 339-367 located in the C-terminal portion of the extracellular domain. When expressed in COS-7 cells, the mutated TSHR (M3B) retained similar TSH binding ability to that of the wild-type receptor. However, the basal cAMP production without TSH stimulation in COS-7 cells transfected with M3B cDNA was significantly higher than that of COS-7 cells with wild-type receptor, indicating that the mutant receptor is constitutively activated. Our results provide new insight into the mechanism of receptor activation. (C) 1995 Academic Press, Inc.

引用

页码：205 / 210

页数：6

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