Cloning and characterization of human urocortin
Cloning and characterization of human urocortin
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DOI：
10.1210/en.137.5.2167
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发表时间：
1996-05-01
期刊：
影响因子：
4.8
通讯作者：
Vale, WW
中科院分区：
文献类型：
--
作者：
Donaldson, CJ;Sutton, SW;Vale, WW
尿皮质素是CRF肽家族的新成员，它还包括尿紧张素I和索瓦蛋白，最近从大鼠中脑中克隆出来。研究发现，尿皮质素的合成复制体与1型和2型CRF受体具有高亲和力，并且基于其在脑内的解剖定位，被认为是2型CRF受体的天然配体。利用基因组文库，我们克隆了人类大鼠尿皮质素的对应体，并将其定位在人类2号染色体上。人和大鼠尿皮质素在成熟肽区有95%的一致性。人工合成的人尿皮质素与1、2 α和2 β型CRF受体高亲和力结合，刺激这些受体稳定转染的细胞积累cAMP，并在体外释放分散的大鼠垂体前叶细胞中的ACTH。此外，CRF结合蛋白与人尿皮质素高亲和力结合，在体外可阻止尿皮质素刺激的ACTH分泌，CRF结合蛋白对人尿皮质素的抑制作用可被生物无活性的CRF片段如CRF阻断（9-33）。
Urocortin, a new member of the CRF peptide family which also includes urotensin I and sauvagine, was recently cloned from the rat midbrain. The synthetic replicate of urocortin was found to bind with high affinity to type 1 and type 2 CRF receptors and, based upon its anatomic localization within the brain, was proposed to be a natural ligand for the type 2 CRF receptors. Using a genomic library, we have cloned the human counterpart of rat urocortin and localized it to human chromosome 2. Human and rat urocortin share 95% identity within the mature peptide region. Synthetic human urocortin binds with high affinity to CRF receptor types 1, 2 alpha, and 2 beta, stimulates cAMP accumulation from cells stably transfected with these receptors, and acts in vitro to release ACTH from dispersed rat anterior pituitary cells. In addition, the CRF-binding protein binds human urocortin with high affinity and can prevent urocortin-stimulated ACTH secretion in vitro, The inhibitory effect of the CRF-binding protein on human urocortin can be blocked by biologically inactive CRF fragments, such as CRF(9-33).