Sphingosine-1-phosphate as a ligand for the G protein coupled receptor EDG-1

Sphingosine-1-phosphate as a ligand for the G protein coupled receptor EDG-1
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DOI:
10.1126/science.279.5356.1552
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发表时间:
1998-03-06
期刊:
影响因子:
56.9
通讯作者:
Hla, T
Hla, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lee, MJ;Van Brocklyn, JR;Hla, T

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鞘脂代谢物鞘氨醇-1-磷酸(SPP)被认为是细胞增殖和存活的第二信使。然而,SPP的许多生物学效应是由于与细胞表面的未知受体结合,SPP激活了异源三聚体鸟嘌呤核苷酸结合蛋白(G蛋白)偶联孤儿受体EDG-1(Endothelial Differentiation Gene-1)是一种与SPP结合的高亲和力受体(解离常数= 8.1nM)和高特异性,EDG-1的过表达诱导过度的细胞-细胞聚集,增强钙粘蛋白的表达,以及以依赖于SPP和小鸟嘌呤核苷酸结合蛋白Rho的方式形成发育良好的粘附连接。
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.