Sphingosine-1-phosphate is a ligand for the G protein-coupled receptor EDG-6

作     者：Van Brocklyn, JR Gräler, MH Bernhardt, G Hobson, JP Lipp, M Spiegel, S 

作者机构：Georgetown Univ Med Ctr Dept Biochem & Mol Biol Washington DC 20007 USA Max Delbruck Ctr Mol Med Dept Tumor Genet & Immunogenet Berlin Germany 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第95卷第8期

页      面：2624-2629页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NCI NIH HHS [CA61774] Funding Source: Medline NIGMS NIH HHS [1 F32 GM19209-01A1, GM43880] Funding Source: Medline 

主　　题：CHO细胞 仓鼠亚科 基因转移技术 配体 溶血磷脂素类 蛋白质结合 放射配体测定 受体 细胞表面/遗传学 受体 细胞表面/代谢 信号传导/药物作用 鞘氨醇/类似物和衍生物 鞘氨醇/代谢 鞘氨醇/药理学 动物 人类 

摘      要：EDG-6 is a recently cloned member of the endothelial differentiation gene (EDG) G protein-coupled receptor family that is expressed in lymphoid and hematopoietic tissue and in the lung. Homology of EDG-6 to the known sphingosine-1-phosphate (SPP) receptors EDG-1, EDG-8, and EDG-5 and lysophosphatidic acid (LPA) receptors EDG-2 and EDG-4 suggested that its ligand may be a lysophospholipid or lysosphingolipid. We examined the binding of [P-32]SPP to HEK293 cells, transiently transfected with cDNA encoding EDG-6, Binding of [P-32]SPP was saturable, demonstrating high affinity (K-D = 63 nmol/L). Binding was also specific for SPP, as only unlabeled SPP and sphinganine-1-phosphate, which lacks the trans double bond at the 4 position, potently displaced radiolabeled SPP, LPA did not compete for binding of SPP at any concentration tested, whereas sphingosylphosphorylcholine competed for binding to EDG-6, but only at very high concentrations. In addition, SPP activated extracellular signal-regulated kinase (Erk) in EDG-6 transfected cells in a pertussis toxin-sensitive manner. These results Indicate that EDG-6 is a high affinity receptor for SPP, which couples to a G(i/o) protein, resulting in the activation of growth-related signaling pathways. (Blood, 2000;95:2624-2629) 2000 by The American Society of Hematology.