Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor
Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor
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DOI：
10.1073/pnas.121165198
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发表时间：
2001-06-19
影响因子：
11.1
通讯作者：
Vale, WW
中科院分区：
文献类型：
--
作者：
Lewis, K;Li, C;Vale, WW
促肾上腺皮质激素释放因子（CRF）家族的神经肽包括哺乳动物肽CRF、尿皮质素和尿皮质素II，以及鱼类的尿紧张素I和蛙类的尿皮质素。哺乳动物肽通过两种G蛋白偶联受体发出信号，调节内分泌、自主神经和应激行为反应，以及一系列外周（心血管、胃肠和免疫）活动。这三种先前已知的配体在解剖学上分布不同，对两种主要受体类型具有不同的特异性。在这里，我们描述了另一种crf相关肽的特征，尿皮质蛋白III。在人和老鼠身上。在公共人类基因组数据库中，我们发现了一个与哺乳动物和鱼类尿皮质素相关肽具有显著序列一致性的部分表达序列标记（EST）克隆。利用基于人类EST序列的引物，从基因组DNA中分离出一个全长的人类克隆体，该克隆体编码一种蛋白质，该蛋白质包含一个推测的与其他已知家族成员结构相关的38-aa肽。然后，我们用人类探针从基因组库中克隆了小鼠的同源基因。人类和小鼠尿皮质素III在38-aa的推定成熟肽中有90%的一致性。在肽编码区，人和小鼠的尿皮质素III与河鲀的尿皮质素相关肽有76%相同，与其他哺乳动物的尿皮质素II、CRF和尿皮质素的亲缘关系更远。小鼠尿皮质素III mRNA表达于下丘脑、杏仁核和脑干等大脑区域，但在小脑、垂体或大脑皮层中不明显，在小肠和皮肤外周也有表达。尿皮质素III对2型CRF受体具有选择性，因此代表了这些受体的另一种潜在内源性配体。
The corticotropin-releasing factor (CRF) family of neuropeptides includes the mammalian peptides CRF, urocortin, and urocortin II, as well as piscine urotensin I and frog sauvagine. The mammalian peptides signal through two G protein-coupled receptor types to modulate endocrine, autonomic, and behavioral responses to stress, as well as a range of peripheral (cardiovascular, gastrointestinal, and immune) activities. The three previously known ligands are differentially distributed anatomically and have distinct specificities for the two major receptor types. Here we describe the characterization of an additional CRF-related peptide, urocortin III. in the human and mouse. In searching the public human genome databases we found a partial expressed sequence tagged (EST) clone with significant sequence identity to mammalian and fish urocortin-related peptides. By using primers based on the human EST sequence, a full-length human clone was isolated from genomic DNA that encodes a protein that includes a predicted putative 38-aa peptide structurally related to other known family members. With a human probe, we then cloned the mouse ortholog from a genomic library. Human and mouse urocortin III share 90% identity in the 38-aa putative mature peptide. In the peptide coding region, both human and mouse urocortin III are 76% identical to pufferfish urocortin-related peptide and more distantly related to urocortin II, CRF, and urocortin from other mammalian species. Mouse urocortin III mRNA expression is found in areas of the brain including the hypothalamus, amygdala, and brainstem, but is not evident in the cerebellum, pituitary, or cerebral cortex: it is also expressed peripherally in small intestine and skin. Urocortin III is selective for type 2 CRF receptors and thus represents another potential endogenous ligand for these receptors.