Edg-6 as a putative sphingosine 1-phosphate receptor coupling to Ca(2+) signaling pathway

Biochem Biophys Res Commun. 2000 Feb 16;268(2):583-9. doi: 10.1006/bbrc.2000.2162.


The endothelial differentiation gene-6 (Edg-6) was recently identified as an orphan G-protein-coupled receptor. Its predicted amino acid sequence is very close to Edg family of receptor proteins whose ligand is supposed to be lysophosphatidic acid (LPA) or lysosphingolipid such as sphingosine 1-phosphate (S1P) and sphingosylphosphorylcholine (SPC). Transfection of the Edg-6 into Chinese hamster ovary (CHO) cells and K562 cells resulted in the appearance of high-affinity [(3)H]S1P binding activity. Among lipids employed, S1P and, even though less potent, SPC, displaced the [(3)H]S1P binding, but LPA was inactive. In Edg-6-transfected CHO cells, an increase in cytosolic Ca(2+) concentration in response to S1P or SPC was clearly enhanced without change in the LPA-induced action as compared with the vector-transfected cells. The enhancement of the Ca(2+) response was associated with a significant accumulation of inositol phosphate, reflecting activation of phospholipase C. Similar enhancement of Ca(2+) response to S1P or SPC was also observed in Edg-6-expressing K562 cells. These lipid-induced actions in CHO cells and K562 cells expressing Edg-6 were markedly suppressed by pertussis toxin treatment. We conclude that Edg-6 is one of S1P or lysosphingolipid receptors that couple to phospholipase C-Ca(2+) system through pertussis toxin-sensitive G-proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Calcium / metabolism*
  • Calcium Signaling*
  • Cricetinae
  • Enzyme Activation
  • Humans
  • K562 Cells
  • Lysophospholipids*
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / metabolism*
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophospholipid
  • Signal Transduction
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism
  • Type C Phospholipases / metabolism


  • Lysophospholipids
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • sphingosine 1-phosphate
  • Type C Phospholipases
  • Sphingosine
  • Calcium