EXPRESSION CLONING OF A HUMAN CORTICOTROPIN-RELEASING-FACTOR RECEPTOR
EXPRESSION CLONING OF A HUMAN CORTICOTROPIN-RELEASING-FACTOR RECEPTOR
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DOI：
10.1073/pnas.90.19.8967
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发表时间：
1993-10-01
影响因子：
11.1
通讯作者：
VALE, WW
中科院分区：
文献类型：
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作者：
CHEN, RP;LEWIS, KA;VALE, WW
促肾上腺皮质激素释放因子（Corticotropin-releasing factor，CRF）是下丘脑-垂体-肾上腺皮质轴的主要神经调节因子，在协调应激和免疫应答的内分泌、自主神经和行为反应中起重要作用。我们在这里报告的克隆的cDNA编码CRF受体从人促肾上腺皮质激素肿瘤库。克隆的cDNA编码一个415-amino add蛋白，包括7个假定的跨膜结构域，并在结构上与降钙素/血管活性肽/生长激素释放激素亚家族的G蛋白偶联受体。COS细胞中表达的受体以高亲和力（K（d）= 3.3 +/- 0.45 nM）和特异性结合大鼠/人CRF，并在功能上与腺苷酸环化酶偶联。CRF拮抗剂α-helCRF-（9-41）抑制CRF刺激的细胞内cAMP增加。北方印迹分析表明，CRF受体在大鼠垂体和脑以及小鼠AtT 20促皮质细胞中表达。 我们还描述了一种选择性剪接形式的受体，其中包括一个插入的29个氨基酸的第一个细胞内环。
Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. We report here the cloning of a cDNA coding for a CRF receptor from a human corticotropic tumor library. The cloned cDNA encodes a 415-amino add protein comprising seven putative membrane-spanning domains and is structurally related to the calcitonin/vasoactive in peptide/growth hormone-releasing hormone subfamily of G protein-coupled receptors. The receptor expressed in COS cells binds rat/human CRF with high affinity (K(d) = 3.3 +/- 0.45 nM and specificity and is functionally coupled to adenylate cyclase. The CRF antagonist alpha-helCRF-(9-41) inhibits the CRF-stimulated increase in intracellular cAMP. Northern blot analysis reveals that the CRF receptor is expressed in the rat pituitary and brain as well as in the mouse AtT20 corticotropic cells. We also describe an alternatively spliced form of the receptor which includes an insert of 29 amino acids in the first intracellular loop.