Laboratory for Cardiovascular Molecular Dynamics, Riken Quantitative Biology Center (QBiC), Furuedai 6-2-3, Suita, Osaka 565-0874, Japan.
J Biochem. 2012 Oct;152(4):305-11. doi: 10.1093/jb/mvs090. Epub 2012 Aug 24.
The lipid mediator sphingosine-1-phosphate (S1P) is generated within cells from sphingosine by two sphingosine kinases (SPHK1 and SPHK2). Intracellularly synthesized S1P is released into the extracellular fluid by S1P transporters, including SPNS2. Released S1P binds specifically to the G protein-coupled S1P receptors (S1PR1/S1P(1)-S1PR5/S1P(5)), which activate a diverse range of downstream signalling pathways. Recent studies have proposed that one of the central physiological functions of intercellular S1P signalling is in lymphocyte trafficking in vivo because genetic disruption of SPHK1/2, SPNS2 or S1PR1/S1P(1) in mice induces a lymphopenia phenotype. In this review, we discuss the current understanding of intercellular S1P signalling in the context of immunity.
脂质介质 1-磷酸鞘氨醇（S1P）由鞘氨醇在细胞内通过两种鞘氨醇激酶（SPHK1 和 SPHK2）生成。细胞内合成的 S1P 通过 S1P 转运蛋白（包括 SPNS2）释放到细胞外液中。释放的 S1P 特异性结合到 G 蛋白偶联的 S1P 受体（S1PR1/S1P（1）-S1PR5/S1P（5）），激活多种下游信号通路。最近的研究表明，细胞间 S1P 信号传递的一个中心生理功能是体内淋巴细胞的迁移，因为在小鼠中基因敲除 SPHK1/2、SPNS2 或 S1PR1/S1P（1）会诱导淋巴细胞减少表型。在这篇综述中，我们讨论了目前对免疫细胞间 S1P 信号传递的理解。
