A splicing isoform of LPP1, LPP1a, exhibits high phosphatase activity toward FTY720 phosphate.
A splicing isoform of LPP1, LPP1a, exhibits high phosphatase activity toward FTY720 phosphate.
复制标题
LPP1 的剪接同工型 LPP1a 对 FTY720 磷酸盐表现出高磷酸酶活性。
DOI：
10.1016/j.bbrc.2008.07.165
复制
发表时间：
2008
影响因子：
3.1
通讯作者：
A. Kihara
中科院分区：
文献类型：
--
作者：
Masao Yamanaka;Yoshihiro Anada;Y. Igarashi;A. Kihara
鞘磷脂代谢产物1-磷酸鞘氨醇(S1P)在胸腺和次级淋巴器官的T细胞输出中起着重要的作用。新型免疫调节剂FTY720在体内被磷酸化为功能形式FTY720磷酸(FTY720-P)，其结构类似于S1P。FTY720-P作为S1P受体激动剂抑制S1P介导的T细胞外流。FTY720-P在血浆中不稳定，被脱磷为FTY720。在本研究中，我们研究了LPP家族成员(LPP1、LPP1a、LPP2和LPP3)对FTY720-P的活性，这些成员表现出广泛的底物特异性。其中，LPP1的剪接异构体LPP1a对FTY720-P的活性最高，亲和力最高。在所测试的面向血液的细胞中，只有内皮细胞对FTY720-P表现出高的磷酸酶活性。LPP1a在血管内皮细胞中有显著的表达，提示LPP1a在血浆FTY720-P的去磷酸化过程中起重要作用。
The sphingolipid metabolite sphingosine 1-phosphate (S1P) plays an essential function in the egress of T cells from the thymus and secondary lymphoid organs. The novel immunomodulating agent FTY720 is phosphorylated in vivo to the functional form FTY720 phosphate (FTY720-P), which is structurally similar to S1P. FTY720-P inhibits the S1P-mediated T cell egress as an agonist of S1P receptors. FTY720-P is not stable in plasma and is dephosphorylated to FTY720. In the present study, we investigated activities toward FTY720-P of LPP family members (LPP1, LPP1a, LPP2, and LPP3), which exhibit broad substrate specificity. Of the four, LPP1a, the splicing isoform of LPP1, had the highest activity toward FTY720-P, and the highest affinity. Among blood-facing cells tested, only endothelial cells displayed high phosphatase activity for FTY720-P. Significant levels of LPP1a expression were found in endothelial cells, suggesting that LPP1a is important for the dephosphorylation of FTY720-P in plasma.
影响因子：
3.1
作者：
Jianhui Zhou;J. Saba
通讯作者：
Jianhui Zhou;J. Saba
DOI：
10.1073/pnas.120146897
发表时间：
2000-07-05
影响因子：
11.1
作者：
Mandala, SM;Thornton, R;Spiegel, S
通讯作者：
Spiegel, S