AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1
AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1
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DOI：
10.1074/jbc.m102743200
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发表时间：
2001-08-03
影响因子：
4.8
通讯作者：
Harrison, DC
中科院分区：
文献类型：
--
作者：
Muir, AI;Chamberlain, L;Harrison, DC
从人脑 cDNA 文库中克隆了一种新型人类 G 蛋白偶联受体，名为 AXOR12，与大鼠孤儿受体 GPR54 有 81% 同源性。哺乳动物细胞中 AXOR12 的异源表达允许鉴定三种替代激动剂肽，它们都具有共同的 C 端酰胺化基序。来自 KiSS-1 基因的肽明显具有高效激动作用，表明存在同源配体，该基因的表达可防止黑色素瘤细胞的转移。采用定量逆转录酶-聚合酶链式反应研究AXOR12和KiSS-1在多种组织中的表达。在大脑、垂体和胎盘中观察到 AXOR12 mRNA 的表达水平最高。在胎盘和大脑中观察到 KiSS-1 基因表达水平最高。生成了针对 AXOR12 C 末端的多克隆抗体，并用于显示受体对小脑、大脑皮层和脑干中神经元的定位。讨论了这些表达模式的生物学意义以及 AXOR12 的推定同源配体的性质。
A novel human G protein-coupled receptor named AXOR12, exhibiting 81% homology to the rat orphan receptor GPR54, was cloned from a human brain cDNA library. Heterologous expression of AXOR12 in mammalian cells permitted the identification of three surrogate agonist peptides, all with a common C-terminal amidated motif. High potency agonism, indicative of a cognate ligand, was evident from peptides derived from the gene KiSS-1, the expression of which prevents metastasis in melanoma cells. Quantitative reverse transcriptase-polymerase chain reaction was used to study the expression of AXOR12 and KiSS-1 in a variety of tissues. The highest levels of expression of AXOR12 mRNA were observed in brain, pituitary gland, and placenta. The highest levels of KiSS-1 gene expression were observed in placenta and brain. A polyclonal antibody raised to the C. terminus of AXOR12 was generated and used to show localization of the receptor to neurons in the cerebellum, cerebral cortex, and brainstem. The biological significance of these expression patterns and the nature of the putative cognate ligand for AXOR12 are discussed.