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Products by the sphingosine kinase/sphingosine 1‐phosphate (S1P) lyase pathway but not S1P stimulate mitogenesis
Author(s) -
Kariya Yuki,
Kihara Akio,
Ikeda Mika,
Kikuchi Fumiaki,
Nakamura Seiichi,
Hashimoto Shunichi,
Choi ChangHwan,
Lee YongMoon,
Igarashi Yasuyuki
Publication year - 2005
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2005.00862.x
Subject(s) - sphingosine , biology , sphingosine kinase , sphingosine kinase 1 , sphingosine 1 phosphate , microbiology and biotechnology , kinase , sphingolipid , cell growth , cell culture , biochemistry , receptor , genetics
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.