Down-regulation of mRNA expression of Edg-3, a putative sphingosine 1-phosphate receptor coupled to phospholipase C-Ca^2+ signaling, during differentiation of HL-60 leukemia cells

• Published in: Japanese Journal of Pharmacology 1999, Vol.79 (suppl.1), p.102-102
• Main Authors: Koichi Sato, Naoya Murata, Junko Kon, Michio Ui, Fumikazu Okajima
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

We reported that sphingosine 1-phosphate (S1P) induced phospholipase C (PLC) activation and Ca^2+ mobilization in HL-60 leukemia cells. To identify the S1P receptor in HL-60 cells, we measured the mRNA expression of the recently identified putative S1P receptors, i.e., Edg-1, AGR16/H218 and Edg-3. Of these putative receptors, Edg-3 mRNA was abundantly expressed, but no significant expression of either Edg-1 mRNA or AGR16/H218 mRNA was detected, in undifferentiated HL-60 cells. Expression of Edg-3 mRNA was markedly down-regulated by inducers of cell differentiation such as dibutyryl cAMP, retinoic acid and 1α, 25-dihydroxyvitamin D_3 , which was associated with the attenuation of the S1P-induced Ca^2+ response. The transfection of Edg-3 cDNA into Chinese hamster ovary (CHO) cells which do not express the Edg-3 mRNA induced an marked increase in the S1P-induced Ca^2+ signaling. We conclude that Edg-3, whose mRNA expression is down-regulated during cell differentiation, may be responsible for the S1P-induced activation of PLC-Ca^2+ system in HL-60 leukemia cells.