IDENTIFICATION OF A 2ND CORTICOTROPIN-RELEASING FACTOR-RECEPTOR GENE AND CHARACTERIZATION OF A CDNA EXPRESSED IN HEART
IDENTIFICATION OF A 2ND CORTICOTROPIN-RELEASING FACTOR-RECEPTOR GENE AND CHARACTERIZATION OF A CDNA EXPRESSED IN HEART
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DOI：
10.1073/pnas.92.7.2969
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发表时间：
1995-03-28
影响因子：
11.1
通讯作者：
VALE, W
中科院分区：
文献类型：
--
作者：
PERRIN, M;DONALDSON, C;VALE, W
促肾上腺皮质激素释放因子（CRF;皮质松素）调节促肾上腺皮质激素（ACTH）和β-内啡肽的分泌，对神经、内分泌、生殖、心血管、胃肠道和免疫系统有广泛的影响。最近，人类、大鼠和小鼠的CRF受体（CRF-R）已被克隆，并在功能和解剖学上进行了表征。我们在此报告了第二个CRF-R cDNA（CRF-RB）的克隆，其编码431个氨基酸的蛋白质，比先前克隆的CRF-R，CRF-RA长16个氨基酸，相似性为68%。CRF-RB以高亲和力结合CRF [Kd = 1.2（0.57-2.5）nM]，并转导CRF刺激的细胞内cAMP积累信号，该信号可被CRF拮抗剂抑制。CRF-RB和以前克隆的受体的氨基酸序列的比较揭示了在N-末端结构域和细胞外环的主要差异，而细胞内环的序列几乎相同。CRF-RB和相关转录物在心脏以及其他组织中表达，包括胃肠道、附睾和脑。
Corticotropin-releasing factor (CRF; corticoliberin) regulates the secretion of corticotropin (ACTH) and beta-endorphin and has a broad range of effects on the nervous, endocrine, reproductive, cardiovascular, gastrointestinal, and immune systems. Recently, human, rat, and mouse CRF receptors (CRF-R) have been cloned and functionally and anatomically characterized, We report here the cloning of a second CRF-R cDNA (CRF-RB), which encodes a protein of 431 amino acids, which is 16 amino acids longer and 68% similar to the previously cloned CRF-R, CRF-RA, When transiently expressed in COS-R 16 cells, CRF-RB binds CRF with high affinity [K-d = 1.2 (0.57-2.5) nM] and transduces the CRF-stimulated signal of the accumulation of intracellular cAMP, which is inhibited by a CRF antagonist. Comparison of the amino acid sequences of CRF-RB and the previously cloned receptor reveals major differences in the N-terminal domain and in the extracellular loops, whereas the sequences of the intracellular loops are nearly identical. CRF-RB and related transcripts are expressed in the heart, as well as in other tissues, including the gastrointestinal tract, epididymis, and brain.