Document Detail

Products by the sphingosine kinase/sphingosine 1-phosphate (S1P) lyase pathway but not S1P stimulate mitogenesis.
MedLine Citation:
PMID:  15938718     Owner:  NLM     Status:  MEDLINE    
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.
Yuki Kariya; Akio Kihara; Mika Ikeda; Fumiaki Kikuchi; Seiichi Nakamura; Shunichi Hashimoto; Chang-Hwan Choi; Yong-Moon Lee; Yasuyuki Igarashi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes to cells : devoted to molecular & cellular mechanisms     Volume:  10     ISSN:  1356-9597     ISO Abbreviation:  Genes Cells     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-07     Completed Date:  2005-08-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9607379     Medline TA:  Genes Cells     Country:  England    
Other Details:
Languages:  eng     Pagination:  605-15     Citation Subset:  IM    
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.
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MeSH Terms
Aldehyde-Lyases / genetics,  metabolism,  pharmacology*
Annexin A5 / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects*
DNA / biosynthesis
Flow Cytometry
Hela Cells
Lysophospholipids / metabolism,  pharmacology*
Models, Biological
Neoplastic Stem Cells
Signal Transduction*
Sphingosine / analogs & derivatives*,  metabolism,  pharmacology
Substrate Specificity
Thymidine / metabolism
Reg. No./Substance:
0/Annexin A5; 0/Lysophospholipids; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate; 50-89-5/Thymidine; 9007-49-2/DNA; EC 4.1.2.-/Aldehyde-Lyases; EC 4.1.2.-/sphingosine 1-phosphate lyase (aldolase)

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