Characterization of two LGR genes homologous to gonadotropin and thyrotropin receptors with extracellular leucine-rich repeats and a G protein-coupled, seven-transmembrane region.
Characterization of two LGR genes homologous to gonadotropin and thyrotropin receptors with extracellular leucine-rich repeats and a G protein-coupled, seven-transmembrane region.
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DOI：
10.1210/mend.12.12.0211
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发表时间：
1998-12
影响因子：
--
通讯作者：
S. Hsu;S. Liang;A. Hsueh
中科院分区：
文献类型：
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作者：
S. Hsu;S. Liang;A. Hsueh
LH、FSH 和 TSH 的受体属于大 G 蛋白偶联七次跨膜 (TM) 蛋白家族，其独特之处在于具有大的 N 末端胞外 (ecto-) 结构域，其中含有富含亮氨酸的重复序列，这对于与糖蛋白配体的相互作用非常重要。我们鉴定了两种新的富含亮氨酸重复序列的 G 蛋白偶联受体，并将它们分别命名为 LGR4 和 LGR5。两种受体的胞外域均含有 17 个富含亮氨酸的重复序列以及 N 端和 C 端侧翼富含半胱氨酸的序列，而已知的糖蛋白激素受体中只有 9 个重复序列。 LGR4 和 LGR5 中富含亮氨酸的重复序列是 24 个氨基酸的阵列，与胰岛素样生长因子 (IGF)/IGF 结合蛋白复合物以及狭缝蛋白、核心蛋白聚糖和 Toll 蛋白的酸不稳定亚基中发现的重复序列相似。 TM 区以及胞外域和 TM 1 之间的连接在 LGR4、LGR5 和来自海葵、苍蝇、线虫、软体动物和哺乳动物的其他 7 个 LGR 中高度保守，表明它们具有共同的进化起源。与促性腺激素和 TSH 受体分别在性腺和甲状腺中的有限组织表达相反，LGR4 在多种组织中表达，包括卵巢、睾丸、肾上腺、胎盘、胸腺、脊髓和甲状腺，而 LGR5 在肌肉、胎盘、脊髓和大脑中发现。基因组DNA杂交分析表明LGR4和LGR5基因在哺乳动物中是保守的。整体氨基酸序列的比较表明，LGR4 和 LGR5 彼此密切相关，但在进化过程中与蜗牛和哺乳动物糖蛋白激素受体中发现的同源受体有所不同。受体基因 LGR 亚家族新成员的鉴定和表征不仅可以在未来分离其配体并了解其生理作用，还可以揭示 G 蛋白偶联受体与富含亮氨酸重复序列的进化关系。
The receptors for LH, FSH, and TSH belong to the large G protein-coupled, seven-transmembrane (TM) protein family and are unique in having a large N-terminal extracellular (ecto-) domain containing leucine-rich repeats important for interaction with the glycoprotein ligands. We have identified two new leucine-rich repeat-containing, G protein-coupled receptors and named them as LGR4 and LGR5, respectively. The ectodomains of both receptors contain 17 leucine-rich repeats together with N- and C-terminal flanking cysteine-rich sequences, compared with 9 repeats found in known glycoprotein hormone receptors. The leucine-rich repeats in LGR4 and LGR5 are arrays of 24 amino acids showing similarity to repeats found in the acid labile subunit of the insulin-like growth factor (IGF)/IGF binding protein complexes as well as slit, decorin, and Toll proteins. The TM region and the junction between ectodomain and TM 1 are highly conserved in LGR4, LGR5, and seven other LGRs from sea anemone, fly, nematode, mollusk, and mammal, suggesting their common evolutionary origin. In contrast to the restricted tissue expression of gonadotropin and TSH receptors in gonads and thyroid, respectively, LGR4 is expressed in diverse tissues including ovary, testis, adrenal, placenta, thymus, spinal cord, and thyroid, whereas LGR5 is found in muscle, placenta, spinal cord, and brain. Hybridization analysis of genomic DNA indicated that LGR4 and LGR5 genes are conserved in mammals. Comparison of overall amino acid sequences indicated that LGR4 and LGR5 are closely related to each other but diverge, during evolution, from the homologous receptor found in snail and the mammalian glycoprotein hormone receptors. The identification and characterization of new members of the LGR subfamily of receptor genes not only allow future isolation of their ligands and understanding of their physiological roles but also reveal the evolutionary relationship of G protein-coupled receptors with leucine-rich repeats.