The secretin G-protein-coupled receptor family: teleost receptors
The secretin G-protein-coupled receptor family: teleost receptors
复制标题
DOI：
10.1677/jme.1.01730
复制
发表时间：
2005-06-01
影响因子：
3.5
通讯作者：
Power, DM
中科院分区：
文献类型：
--
作者：
Cardoso, JCR;Clark, MS;Power, DM
通过河豚基因组联盟数据库的定向克隆和数据挖掘，鉴定出了 G 蛋白偶联受体 (GPCR) 促胰液素家族（家族 2）的 21 个成员，这是迄今为止对硬骨鱼中促胰液素 GPCR 的最全面的描述。许多家族成员都发现了重复基因，即垂体腺苷酸环化酶激活多肽（PACAP）/血管活性肠肽（VIP）、降钙素、降钙素基因相关肽（CGRP）、生长激素释放激素（GHRH）、胰高血糖素受体/胰高血糖素样肽（GLP）和甲状旁腺激素相关肽（PTHrP）/PTH的受体。对其他硬骨鱼基因组（斑马鱼和四齿鱼）的挖掘表明，在塔基东方鲀基因组中发现的重复基因也存在于这些鱼类中。对大肠杆菌、酵母、果蝇、秀丽隐杆线虫和玻璃海鞘基因组的其他数据库搜索表明，GPCR 家族 2 仅存在于多细胞生物中。除促胰液素本身外，所有人类促胰液素受体的直系同源物均已被鉴定。河豚基因组联盟数据库中的其他数据库搜索也未能揭示促胰液素配体，因此假设受体和配体都是在硬骨鱼/四足动物谱系分化后进化的。蛋白质和 DNA 水平的系统发育分析为每个受体家族分组提供了强有力的支持，但群体之间的支持较弱，这使得进化推断变得困难。对 PACAP/VIP 受体家族的更严格的分析证实了先前的假设，即血管活性肠肽受体 (VPAC(1)R) 基因是该受体的祖先形式。
Twenty-one members of the secretin family (family 2) of G-protein-coupled receptors (GPCRs) were identified via directed cloning and data-mining of the Fugu Genome Consortium database, representing the most comprehensive description of secretin GPCRs in a teleost fish to date. Duplicated genes were identified for many of the family members, namely the receptors for pituitary adenylate cyclase-activating polypeptide (PACAP)/vasoactive intestinal peptide (VIP), calcitonin, calcitonin gene-related peptide (CGRP), growth hormone releasing hormone (GHRH), glucagon receptor/glucagon-like peptide (GLP) and parathyroid hormone-related peptide (PTHrP)/PTH. Mining of other teleost genomes (zebrafish and Tetraodon) revealed that the duplicated genes identified in the Takifugu genome were also present in these fish. Additional database searching of the Escherichia coli, yeast, Drosophila, Caenorhabditis elegans and Ciona genomes revealed that the family 2 of GPCRs were only present in the multicellular organisms. Orthologues of all the human secretin receptors were identified with the exception of secretin itself. Additional database searches in the Fugu Genome Consortium database also failed to reveal a secretin ligand and so it is hypothesised that both the receptor and the ligand evolved after the divergence of teleost/tetrapod lineages. Phylogenetic analysis at both the protein and the DNA level provided strong support for each of the individual receptor family groupings, but weak support between groups, making evolutionary inferences difficult. A more critical analysis of the PACAP/VIP receptor family confirmed previous hypotheses that the vasoactive intestinal peptide receptor (VPAC(1)R) gene is the ancestral form of the receptor.