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

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+)](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 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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Cell Line
  • Dose-Response Relationship, Drug
  • Humans
  • Ligands
  • Lysophospholipids / chemistry
  • Lysophospholipids / pharmacology*
  • Molecular Sequence Data
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophosphatidic Acid
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Spodoptera
  • Structure-Activity Relationship
  • Substrate Specificity
  • Transfection


  • Ligands
  • Lysophospholipids
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophosphatidic Acid
  • Recombinant Fusion Proteins
  • Calcium

Associated data

  • GENBANK/AF233092