Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species

FEBS Letters

Bandoh, Koji¹  Tsujimoto, Masafumi²  Arai, Hiroyuki¹  Inoue, Keizo¹  Taira, Akitsu¹  Aoki, Junken¹ 

[1] Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;Laboratory of Cellular Biochemistry, The Institute of Physical and Chemical Research (RIKEN), 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan

关键词: Lysophosphatidic acid;    Endothelial cell differentiation gene family;    EDG2;    EDG4;    EDG7;    EDG;    endothelial cell differentiation gene;    LPA;    lysophosphatidic acid;    S1P;    sphingosine 1-phosphate;    alkyl-GP;    1-alkyl-2-lyso-sn-glycero-3-phosphate;    alkenyl-GP;    1-alkenyl-2-lyso-sn-glycero-3-phosphate;    GPCR;    G protein-coupled receptor;    [Ca2+]i;    intracellular concentration of Ca2+ ion;    1-acyl-LPA;    1-acyl-2-lysophosphatidic acid;    2-acyl-LPA;    2-acyl-1-lysophosphatidic acid;   

DOI  :  10.1016/S0014-5793(00)01827-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Δ9-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 Δ9 position of octadecanoyl residues, since 2-elaidoyl (18:1, trans) and 2-petroselinoyl (18:1, cis-Δ12) LPA were poor ligands for EDG7. In conclusion, the present study demonstrates that each LPA receptor can be activated differentially by the LPA species.

【 授权许可】

Unknown