Constitutive activation of the TSH receptor by spontaneous mutations affecting the N‐terminal extracellular domain

FEBS Letters

Parma, Jasmine³  Duprez, Laurence¹  Hermans, Jacques²  Dumont, Jacques E¹  Costagliola, Sabine¹  Vassart, Gilbert¹  Van Sande, Jacqueline¹ 

[1] Institut de Recherche Interdisciplinaire, Faculty of Medicine, University of Brussels, Brussels, Belgium;Centre Hospitalier de Jolimont, Haine-Saint-Paul, Belgium;Service de Génétique Médicale, Hôpital Erasme, University of Brussels, Brussels, Belgium

关键词: TSH receptor;    Activating mutation;    Extracellular domain;    Model of activation;   

DOI  :  10.1016/S0014-5793(97)00532-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Activating mutations of the TSH receptor gene have been found in toxic adenomas and hereditary toxic thyroid hyperplasia. Up to now, all mutations have been located in the serpentine portion of the receptor. We now describe two additional mutations affecting Ser-281 (Ser-281-Thr and Ser-281-Asn) in the ectodomain of the receptor. After transfection in COS cells, both mutants displayed increased constitutive activity for cAMP generation despite expression at a lower level than the wild type. The mutants were responsive to TSH. The present results are compatible with a model in which the activity of the unliganded receptor is kept at a low level by an inhibitory interaction between the N-terminal domain and the serpentine portion of the receptor.

【 授权许可】

Unknown