Bandoh K, Aoki J, Taira A, Tsujimoto M, Arai H, Inoue K
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
FEBS Lett. 2000 Jul 28;478(1-2):159-65. doi: 10.1016/s0014-5793(00)01827-5.
We examined the structure-activity relationship of cloned lysophosphatidic acid (LPA) receptors (endothelial cell differentiation gene (EDG) 2, EDG4, and EDG7) by measuring Ca(2+) in Sf9 insect cells expressing each receptor using LPA with various acyl chains bound at either the sn-1 or the sn-2 position of the glycerol backbone. For EDG7 the highest reactivity was observed with LPA with Delta9-unsaturated fatty acid (oleic (18:1), linoleic (18:2), and linolenic (18:3)) at sn-2 followed by 2-palmitoleoyl (16:1) and 2-arachidonoyl (20:4) LPA. In contrast, EDG2 and EDG4 showed broad ligand specificities, although EDG2 and EDG4 discriminated between 14:0 (myristoyl) and 16:0 (palmitoyl), and 12:0 (lauroyl) and 14:0 LPAs, respectively. EDG7 recognizes the cis double bond at the Delta9 position of octadecanoyl residues, since 2-elaidoyl (18:1, trans) and 2-petroselinoyl (18:1, cis-Delta12) LPA were poor ligands for EDG7. In conclusion, the present study demonstrates that each LPA receptor can be activated differentially by the LPA species.
我们通过使用在甘油主链的sn-1或sn-2位置结合有各种酰基链的溶血磷脂酸（LPA），在表达每种受体的Sf9昆虫细胞中测量Ca(2+)，研究了克隆的溶血磷脂酸（LPA）受体（内皮细胞分化基因（EDG）2、EDG4和EDG7）的构效关系。对于EDG7，在sn-2位置具有Δ9-不饱和脂肪酸（油酸（18:1）、亚油酸（18:2）和亚麻酸（18:3））的LPA反应性最高，其次是2-棕榈油酰基（16:1）和2-花生四烯酰基（20:4）LPA。相比之下，EDG2和EDG4表现出广泛的配体特异性，尽管EDG2和EDG4分别区分了14:0（肉豆蔻酰基）和16:0（棕榈酰基），以及12:0（月桂酰基）和14:0 LPA。EDG7识别十八烷酰基残基Δ9位置的顺式双键，因为2-反式油酰基（18:1，反式）和2-岩芹酰基（18:1，顺式-Δ12）LPA是EDG7的不良配体。总之，本研究表明每种LPA受体可被不同种类的LPA差异激活。
