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

• Published in: Biochemical and biophysical research communications Vol. 268; no. 2; pp. 583 - 589
• Main Authors: Yamazaki, Y, Kon, J, Sato, K, Tomura, H, Sato, M, Yoneya, T, Okazaki, H, Okajima, F, Ohta, H
• Format: Journal Article
• Language: English
• Published: United States 16.02.2000
• Subjects: Animals; Calcium - metabolism; Calcium Signaling; CHO Cells; 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
• ISSN: 0006-291X
• 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.