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

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 recept or 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 obse rved 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 s pecificities, 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 res idues, since 2-elaidoyl (18:1, tr ans) and 2 -petroselinoyl (18:1, cis-Delt a 12) LPA were poor Ligands for EDG7, In conclusion, the present study demo nstrates that each LPA receptor can be activated differentially by the LPA species. (C) 2000 Federation of European Biochemical Societies. Published b y Elsevier Science B.V. All rights reserved.