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

[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.

[学科分类] 生物化学/生物物理

[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