An autocrine sphingosine-1-phosphate signaling loop enhances NF-kappaB-activation and survival.
An autocrine sphingosine-1-phosphate signaling loop enhances NF-kappaB-activation and survival.
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DOI：
10.1186/1471-2121-11-45
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发表时间：
2010-06-24
期刊：
影响因子：
--
通讯作者：
Törnquist K
中科院分区：
文献类型：
--
作者：
Blom T;Bergelin N;Meinander A;Löf C;Slotte JP;Eriksson JE;Törnquist K
鞘氨醇-1-磷酸（S1P）是一种生物活性脂质，调节多种细胞功能，包括细胞增殖、存活、迁移和血管生成。S1P通过G蛋白偶联受体（gpcr）信号传导或通过细胞内作用方式介导其作用。在这项研究中，我们研究了s1p诱导的生存信号传导的机制。我们发现S1P以NF-κB依赖的方式保护fasl诱导的细胞死亡。NF-κB通过S1P2受体和Gi蛋白信号被胞外S1P激活。我们的研究还表明，胞外S1P刺激细胞快速产生和分泌额外的S1P，从而进一步放大NF-κB的活化。我们提出了一个自分泌S1P的自扩增环，具有增强细胞存活的能力。该机制提供了对S1P在正常发育和癌变过程中调节细胞命运的多方面作用的进一步了解。
Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates a multitude of cellular functions, including cell proliferation, survival, migration and angiogenesis. S1P mediates its effects either by signaling through G protein-coupled receptors (GPCRs) or through an intracellular mode of action. In this study, we have investigated the mechanism behind S1P-induced survival signalling. We found that S1P protected cells from FasL-induced cell death in an NF-κB dependent manner. NF-κB was activated by extracellular S1P via S1P2 receptors and Gi protein signaling. Our study also demonstrates that extracellular S1P stimulates cells to rapidly produce and secrete additional S1P, which can further amplify the NF-κB activation. We propose a self-amplifying loop of autocrine S1P with capacity to enhance cell survival. The mechanism provides increased understanding of the multifaceted roles of S1P in regulating cell fate during normal development and carcinogenesis.
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1-磷酸盐的出口和功能。
DOI：
10.1016/j.bbalip.2009.02.011
发表时间：
2009-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Kim RH;Takabe K;Milstien S;Spiegel S
通讯作者：
Spiegel S
DOI：
10.1126/science.1176709
发表时间：
2009-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hait NC;Allegood J;Maceyka M;Strub GM;Harikumar KB;Singh SK;Luo C;Marmorstein R;Kordula T;Milstien S;Spiegel S
通讯作者：
Spiegel S
影响因子：
4.8
作者：
Blom, T;Slotte, JP;Törnquist, K
通讯作者：
Törnquist, K
影响因子：
4.1
作者：
Balthasar, Sonja;Samulin, Johanna;Tornquist, Kid
通讯作者：
Tornquist, Kid
影响因子：
4.8
作者：
Billich, A;Bornancin, F;Baumruker, T
通讯作者：
Baumruker, T