Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species - Structure-activity relationship of cloned LPA receptors

Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species - Structure-activity relationship of cloned LPA receptors
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DOI:
10.1016/s0014-5793(00)01827-5
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发表时间:
2000-07-28
期刊:
影响因子:
3.5
通讯作者:
Inoue, K
Inoue, K
中科院分区:
生物学3区
文献类型:
--
作者:
Bandoh, K;Aoki, J;Inoue, K

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我们研究了克隆的溶血磷脂酸(LPA)受体的结构-活性关系(i)在表达每种受体的Sf 9昆虫细胞中,使用具有结合在甘油骨架的sn-1或sn-2位的各种酰基链的LPA测量[Ca 2 +],对于EDG 7,观察到与在sn-2处具有δ 9-不饱和脂肪酸(油酸(18:1)、亚油酸(18:2)和亚麻酸(18:3))的LPA的最高反应性,然后是2-棕榈油酰基(16:1)和2-花生四烯酰基(20:4)LPA。相反,EDG 2和EDG 4显示出广泛的配体特异性,尽管EDG 2和EDG 4分别区分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。EDG 7识别十八烷酰基残基的Δ 9位置处的顺式双键,因为2-elaidoyl(18:1,反式)和2 -petroselinoyl(18:1,顺式-Δ 12)LPA是EDG 7的不良配体。(C)2000年欧洲生物化学学会联合会。由Elsevier Science B. V.出版,版权所有。
We examined the structure-activity relationship of cloned lysophosphatidic acid (LPA) receptors (endothelial cell differentiation gene (EDG) 2, EDG4, and EDG7) by measuring [Ca2+](i) 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 Delta 9-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 Delta 9 position of octadecanoyl residues, since 2-elaidoyl (18:1, tr ans) and 2 -petroselinoyl (18:1, cis-Delta 12) LPA were poor Ligands for EDG7, In conclusion, the present study demonstrates that each LPA receptor can be activated differentially by the LPA species. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.