MOLECULAR-CLONING OF THE THYROTROPIN RECEPTOR

MOLECULAR-CLONING OF THE THYROTROPIN RECEPTOR
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DOI:
10.1126/science.2556796
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发表时间:
1989-12-22
期刊:
影响因子:
56.9
通讯作者:
VASSART, G
VASSART, G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
PARMENTIER, M;LIBERT, F;VASSART, G

文献摘要

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促甲状腺激素(TSH)是调节甲状腺的主要生理因子。用与G蛋白偶联受体基因序列相似的DNA片段进行选择性扩增,克隆了促甲状腺激素受体(TSHR)。在从基因组DNA中获得的11个新的受体克隆中,有一个具有不同于所有其他克隆的序列特征。尽管该克隆不与甲状腺转录本杂交,但对狗甲状腺互补DNA文库的中等严格性筛选发现了一个编码4.9kb的甲状腺特异转录本的cDNA.该转录本编码的多肽由一个398个氨基酸残基的氨基末端组成,构成一个推测的胞外结构域,连接到一个346个残基的羧基末端结构域,包含7个假定的跨膜片段。该基因的表达赋予非洲爪哇卵母细胞和Y1细胞对TSH的反应性,对COS细胞具有TSH结合表型。TSHR和黄体生成素受体-绒毛膜促性腺激素构成G蛋白偶联受体亚家族,具有明显的序列特征。
The pituitary hormone thyrotropin, or thyroid-stimulating hormone (TSH), is the main physiological agent that regulates the thyroid gland. The thyrotropin receptor (TSHR) was cloned by selective amplification with the polymerase chain reaction of DNA segments presenting sequence similarity with genes for G protein-coupled receptors. Out of 11 new putative receptor clones obtained from genomic DNA, one had sequence characteristics different from all the others. Although this clone did not hybridize to thyroid transcripts, screening of the dog thyroid complementary DNA (cDNA) library at moderate stringency identified a cDNA encoding a 4.9-kilobase thyroid-specific transcript. The polypeptide encoded by this thyroid-specific transcript consisted of a 398-amino acid residue amino-terminal segment, constituting a putative extracellular domain, connected to a 346-residue carboxyl-terminal domain that contained seven putative transmembrane segments. Expression of the cDNA conferred TSH responsiveness to Xenopus oocytes and Y1 cells and a TSH binding phenotype to COS cells. The TSHR and the receptor for luteinizing hormone-choriogonadotropin constitute a subfamily of G protein-coupled receptors with distinct sequence characteristics.