Lee M J, Van Brocklyn J R, Thangada S, Liu C H, Hand A R, Menzeleev R, Spiegel S, Hla T
Department of Physiology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
Science. 1998 Mar 6;279(5356):1552-5. doi: 10.1126/science.279.5356.1552.
The sphingolipid metabolite sphingosine-1-phosphate (SPP) has been implicated as a second messenger in cell proliferation and survival. However, many of its biological effects are due to binding to unidentified receptors on the cell surface. SPP activated the heterotrimeric guanine nucleotide binding protein (G protein)-coupled orphan receptor EDG-1, originally cloned as Endothelial Differentiation Gene-1. EDG-1 bound SPP with high affinity (dissociation constant = 8.1 nM) and high specificity. Overexpression of EDG-1 induced exaggerated cell-cell aggregation, enhanced expression of cadherins, and formation of well-developed adherens junctions in a manner dependent on SPP and the small guanine nucleotide binding protein Rho.
鞘脂代谢产物1-磷酸鞘氨醇（SPP）被认为是细胞增殖和存活过程中的第二信使。然而，其许多生物学效应是由于与细胞表面未明确的受体结合所致。SPP激活了异三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）偶联的孤儿受体EDG-1，该受体最初作为内皮分化基因-1被克隆。EDG-1以高亲和力（解离常数 = 8.1 nM）和高特异性结合SPP。EDG-1的过表达以依赖于SPP和小GTP结合蛋白Rho的方式诱导过度的细胞间聚集、钙黏蛋白表达增强以及形成发育良好的黏附连接。
