Goetzl E J, An S
Department of Medicine, University of California Medical Center, San Francisco 94143-0711, USA.
Adv Exp Med Biol. 1999;469:259-64. doi: 10.1007/978-1-4615-4793-8_38.
The results of molecular cloning and homology searches have identified a minimum of five different proteins of the endothelial differentiation gene (edg) encoded subfamily of GPCRs. Edg protein GPCRs show amino acid sequence identity of 31% to 34% as a subfamily, but contain two homology clusters with greater similarity of structures and functions. One cluster of high amino acid sequence homology includes Edg-2 and Edg-4 proteins, that encode GPCRs for LPA, but not lysosphingolipids. A second homology cluster encompasses Edg-1, Edg-3 and Edg-5. Edg-3 and Edg-5 encode GPCRs specific for S1P, but not LPA. Preliminary data suggest that Edg-1 encodes a GPCR for S1P and one or more other lysosphingolipids, but the signals evoked by S1P alone are far weaker than those transduced by Edg-3 and Edg-5. Similarities of the structures of genes for the respective homology clusters supports this tentative classification of the Edg protein GPCRs. Future research will be directed to completion of the elucidation of genomic organization and signaling pathways, and a greater understanding of the breadth of functional roles of Edg proteins in development and activities of the nervous, cardiovascular, endocrine and immune systems.
分子克隆和同源性搜索结果已鉴定出内皮分化基因（edg）编码的GPCR亚家族中至少五种不同的蛋白质。作为一个亚家族，Edg蛋白GPCR的氨基酸序列同一性为31%至34%，但包含两个结构和功能相似性更高的同源簇。一个高氨基酸序列同源性簇包括Edg-2和Edg-4蛋白，它们编码LPA的GPCR，但不编码溶血鞘脂的GPCR。第二个同源簇包括Edg-1、Edg-3和Edg-5。Edg-3和Edg-5编码对S1P特异的GPCR，但对LPA不特异。初步数据表明，Edg-1编码一种对S1P和一种或多种其他溶血鞘脂特异的GPCR，但单独由S1P引发的信号远弱于由Edg-3和Edg-5转导的信号。各个同源簇基因结构的相似性支持了Edg蛋白GPCR的这种初步分类。未来的研究将致力于完成基因组组织和信号通路的阐明，并更深入地了解Edg蛋白在神经、心血管、内分泌和免疫系统的发育和活动中的功能作用广度。
