title: Products by the sphingosine kinase/sphingosine 1-phosphate (S1P) lyase pathway but not S1P stimulate mitogenesis.
abstract: Sphingosine 1-phosphate (S1P) functions as a ligand for the S1P/EDG family receptors. For years, intracellular signaling roles for S1P have also been suggested, especially in cell proliferation. Now, we have generated several mouse F9 embryonic carcinoma cell lines varying in expression of the S1P-degrading enzyme, S1P lyase (SPL) and/or sphingosine kinase (SPHK1). All these cell lines accumulated S1P compared to the wild-type F9 cells, but the amounts varied. We investigated the ability of these cells to proliferate under low serum conditions, as measured by a thymidine uptake assay. Although F9 cells over-expressing SPHK1 did exhibit enhanced DNA synthesis, other S1P-accumulating cells (SPL-null cells and SPL-null cells over-expressing SPHK1) did not. The overproduction of both SPL and SPHK1 resulted in the most striking mitogenic effect. Moreover, nM concentrations of sphingosine (or dihydrosphingosine) stimulated DNA synthesis in an SPL-dependent manner. These results indicate that products by the SPL pathway, not S1P itself, function in mitogenesis.
authors.affiliation: Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kariya
authors.forename: Akio
authors.initials: A
authors.lastname: Kihara
authors.forename: Mika
authors.initials: M
authors.lastname: Ikeda
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Kikuchi
authors.forename: Seiichi
authors.initials: S
authors.lastname: Nakamura
authors.forename: Shunichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Choi
authors.forename: Yong-Moon
authors.initials: YM
authors.lastname: Lee
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Igarashi
mesh_terms: D000446:Aldehyde-Lyases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D014411:Neoplastic Stem Cells; D010957:Plasmids; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013379:Substrate Specificity; D013936:Thymidine / Q000378:metabolism; D014162:Transfection
chemical_list: D017304:Annexin A5; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D004247:DNA; D000446:Aldehyde-Lyases; C022649:sphingosine 1-phosphate lyase (aldolase); D013110:Sphingosine; D013936:Thymidine