Products by the sphingosine kinase/sphingosine 1-phosphate (S1P) lyase pathway but not S1P stimulate mitogenesis
Products by the sphingosine kinase/sphingosine 1-phosphate (S1P) lyase pathway but not S1P stimulate mitogenesis
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DOI：
10.1111/j.1365-2443.2005.00862.x
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发表时间：
2005-06-01
期刊：
影响因子：
2.1
通讯作者：
Igarashi, Y
中科院分区：
文献类型：
--
作者：
Kariya, Y;Kihara, A;Igarashi, Y
Sphingosine 1-phosphate （S1P）是S1P/EDG家族受体的配体。多年来，也有人提出S1P在细胞内的信号传导作用，特别是在细胞增殖中。现在，我们已经生成了几种不同表达S1P降解酶、S1P裂解酶（SPL）和/或鞘氨酸激酶（SPHK1）的小鼠F9胚胎癌细胞系。与野生型F9细胞相比，所有细胞系都积累了S1P，但数量不同。我们研究了这些细胞在低血清条件下增殖的能力，通过胸腺嘧啶摄取测定。虽然过表达SPHK1的F9细胞确实表现出增强的DNA合成，但其他积累sp1的细胞（无spl细胞和过表达SPHK1的无spl细胞）没有。SPL和SPHK1的过量产生导致了最显著的有丝分裂效应。此外，纳米浓度的鞘氨醇（或二氢鞘氨醇）以spl依赖的方式刺激DNA合成。这些结果表明SPL途径的产物，而不是S1P本身，在有丝分裂发生中起作用。
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.