The Sphingosine 1-Phosphate Transporter, SPNS2, Functions as a Transporter of the Phosphorylated Form of the Immunomodulating Agent FTY720
The Sphingosine 1-Phosphate Transporter, SPNS2, Functions as a Transporter of the Phosphorylated Form of the Immunomodulating Agent FTY720
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DOI：
10.1074/jbc.m110.171116
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发表时间：
2011-01-21
影响因子：
4.8
通讯作者：
Nishi, Tsuyoshi
中科院分区：
文献类型：
--
作者：
Hisano, Yu;Kobayashi, Naoki;Nishi, Tsuyoshi
FTY 720是一种新型免疫调节药物，可在细胞内磷酸化;其磷酸化形式FTY 720-P与1-磷酸鞘氨醇（S1 P）受体S1 P（1）结合，并抑制淋巴细胞进入循环血液。虽然FTY 720-P的药理作用的重要性已被充分认识，但关于FTY 720-P在细胞内磷酸化后如何从细胞中释放的知之甚少。之前，我们发现斑马鱼Spns 2可以作为细胞的S1 P出口商，并且对斑马鱼心脏形成至关重要。在这里，我们证明了人SPNS 2可以运输几种S1 P类似物，包括FTY 720-P。此外，FTY 720-P通过与S1 P相同的途径被SPNS 2运输。这是第一次在细胞中鉴定FTY 720-P转运蛋白;这一发现对于理解FTY 720代谢很重要。
FTY720 is a novel immunomodulating drug that can be phosphorylated inside cells; its phosphorylated form, FTY720-P, binds to a sphingosine 1-phosphate (S1P) receptor, S1P(1), and inhibits lymphocyte egress into the circulating blood. Although the importance of its pharmacological action has been well recognized, little is known about how FTY720-P is released from cells after its phosphorylation inside cells. Previously, we showed that zebrafish Spns2 can act as an S1P exporter from cells and is essential for zebrafish heart formation. Here, we demonstrate that human SPNS2 can transport several S1P analogues, including FTY720-P. Moreover, FTY720-P is transported by SPNS2 through the same pathway as S1P. This is the first identification of an FTY720-P transporter in cells; this finding is important for understanding FTY720 metabolism.