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Genes to Cells (2005) 10, 605-615. doi:10.1111/j.1365-2443.2005.00862.x
© 2005 Blackwell Publishing or its licensors

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Products by the sphingosine kinase/sphingosine 1-phosphate (S1P) lyase pathway but not S1P stimulate mitogenesis

Yuki Kariya1, Akio Kihara1, Mika Ikeda1, Fumiaki Kikuchi2, Seiichi Nakamura2, Shunichi Hashimoto2, Chang-Hwan Choi3, Yong-Moon Lee3 and Yasuyuki Igarashi1,*

1 Department of Biomembrane and Biofunctional Chemistry, and 2 Department of Synthetic and Industrial Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan
3 College of Pharmacy, Chungbuk National University, Chongju 361-763, South Korea

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.


Communicated by: Yoshinori Ohsumi

* Correspondence: E-mail: yigarash{at}pharm.hokudai.ac.jp




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