Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival.
Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival.
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鞘氨醇激酶表达会增加细胞内鞘氨醇1-磷酸盐，并促进细胞生长和存活。
DOI：
10.1083/jcb.147.3.545
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发表时间：
1999-11-01
期刊：
影响因子：
--
通讯作者：
Spiegel S
中科院分区：
文献类型：
--
作者：
Olivera A;Kohama T;Edsall L;Nava V;Cuvillier O;Poulton S;Spiegel S
鞘氨醇-1-磷酸（SPP）是一种生物活性脂质，最近被鉴定为G蛋白偶联细胞表面受体EDG家族的配体。然而，外源性SPP的促有丝分裂和存活作用可能与结合细胞表面受体无关（货车Brocklyn，J.R.，M.J. Lee，R. Menzeleev，A.奥利维拉湖Edsall，O. Cuvillier，D. M.放大图片作者：托马斯，P. J. P. Thangada，T. Hla和S.《明镜周刊》1998. 142：229-240）。鞘氨醇激酶是一种与SPP形成有关的独特的脂质激酶，它的克隆为研究胞内SPP的作用提供了新的工具。鞘氨醇激酶的表达显著增加了NIH 3 T3成纤维细胞和HEK 293细胞中SPP的水平，但没有观察到SPP分泌到培养基中。NIH 3 T3成纤维细胞中鞘氨醇激酶活性的增加足以促进低血清培养基中的生长，加速G1/S转换，并增加DNA合成和细胞周期S期细胞的比例，同时伴随细胞数量的增加。鞘氨醇激酶在NIH 3 T3成纤维细胞或HEK 293细胞中的瞬时或稳定过表达可保护细胞免受血清剥夺或神经酰胺升高诱导的细胞凋亡。N，N-二甲基鞘氨醇是鞘氨醇激酶的竞争性抑制剂，可阻断鞘氨醇激酶过表达对细胞增殖和凋亡的抑制作用。与此相反，百日咳毒素并没有消除这些生物反应。在Jurkat T细胞中，鞘氨醇激酶的过表达也抑制血清剥夺和神经酰胺诱导的细胞凋亡，并在较小程度上，Fas诱导的细胞凋亡，这与DEVDase活性的抑制，以及抑制的执行caspase-3。结合大量证据表明生长和存活因子激活鞘氨醇激酶，我们的结果表明SPP作为细胞生长和存活的重要第二信使发挥作用。因此，SPP属于一类新的脂质介质，可以在细胞内外发挥作用。
Sphingosine-1-phosphate (SPP) is a bioactive lipid that has recently been identified as the ligand for the EDG family of G protein–coupled cell surface receptors. However, the mitogenic and survival effects of exogenous SPP may not correlate with binding to cell-surface receptors (Van Brocklyn, J.R., M.J. Lee, R. Menzeleev, A. Olivera, L. Edsall, O. Cuvillier, D.M. Thomas, P.J.P. Coopman, S. Thangada, T. Hla, and S. Spiegel. 1998. J. Cell Biol. 142:229–240). The recent cloning of sphingosine kinase, a unique lipid kinase responsible for the formation of SPP, has provided a new tool to investigate the role of intracellular SPP. Expression of sphingosine kinase markedly increased SPP levels in NIH 3T3 fibroblasts and HEK293 cells, but no detectable secretion of SPP into the medium was observed. The increased sphingosine kinase activity in NIH 3T3 fibroblasts was sufficient to promote growth in low- serum media, expedite the G1/S transition, and increase DNA synthesis and the proportion of cells in the S phase of the cell cycle with a concomitant increase in cell numbers. Transient or stable overexpression of sphingosine kinase in NIH 3T3 fibroblasts or HEK293 cells protected against apoptosis induced by serum deprivation or ceramide elevation. N,N-Dimethylsphingosine, a competitive inhibitor of sphingosine kinase, blocked the effects of sphingosine kinase overexpression on cell proliferation and suppression of apoptosis. In contrast, pertussis toxin did not abrogate these biological responses. In Jurkat T cells, overexpression of sphingosine kinase also suppressed serum deprivation- and ceramide-induced apoptosis and, to a lesser extent, Fas-induced apoptosis, which correlated with inhibition of DEVDase activity, as well as inhibition of the executionary caspase-3. Taken together with ample evidence showing that growth and survival factors activate sphingosine kinase, our results indicate that SPP functions as a second messenger important for growth and survival of cells. Hence, SPP belongs to a novel class of lipid mediators that can function inside and outside cells.
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凋亡过程中拆卸细胞 - 细胞接触与β-catenin的caspase依赖性蛋白水解裂解耦合。
影响因子：
7.8
作者：
Brancolini, C;Lazarevic, D;Rodriguez, J;Schneider, C
通讯作者：
Schneider, C
影响因子：
4.8
作者：
Kon, J;Sato, K;Okajima, F
通讯作者：
Okajima, F
影响因子：
4.8
作者：
Kohama, T;Olivera, A;Spiegel, S
通讯作者：
Spiegel, S
影响因子：
4.8
作者：
CORONEOS, E;MARTINEZ, M;KESTER, M
通讯作者：
KESTER, M
DOI：
10.1016/0005-2760(96)00092-6
发表时间：
1996-10-18
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子：
--
作者：
Buehrer, BM;Bardes, ES;Bell, RM
通讯作者：
Bell, RM