FTY720‐phosphate is dephosphorylated by lipid phosphate phosphatase 3
FTY720‐phosphate is dephosphorylated by lipid phosphate phosphatase 3
复制标题
FTY720-磷酸被脂质磷酸磷酸酶 3 去磷酸化
DOI：
10.1016/j.febslet.2007.05.069
复制
发表时间：
2007
期刊：
影响因子：
3.5
通讯作者：
A. Billich
中科院分区：
文献类型：
--
作者：
D. Mechtcheriakova;Alexander Wlachos;Jury Sobanov;F. Bornancin;G. Zlabinger;T. Baumruker;A. Billich
FTY 720是一种新型的免疫调节药物，对多发性硬化症的治疗有效。该药物在体内通过鞘氨醇激酶2转化为单磷酸FTY 720-P。这种转化是不完全的，表明激酶和磷酸酶活性的相反作用。为了解决哪些已知的脂质磷酸酶可能使FTY 720-P去磷酸化，我们在HEK 293细胞中过表达了广泛特异性脂质磷酸酶LPP 1 -3和特异性S1 P磷酸酶（SPP 1和2），并使用转染细胞的裂解物进行了体外测定。在LPP中，只有LPP 3能够使FTY 720-P去磷酸化;在SPP中，只有SPP 1显示出对FTY 720-P的活性。在完整细胞上，LPP 3充当外磷酸酶或FTY 720-P，因此代表了体内观察到的FTY 720和FTY 720-P之间的平衡所涉及的主要磷酸酶。
FTY720 is a novel immunomodulatory drug efficacious in the treatment of multiple sclerosis. The drug is converted in vivo to the monophosphate, FTY720-P, by sphingosine kinase 2. This conversion is incomplete, suggesting opposing actions of kinase and phosphatase activities. To address which of the known lipid phosphatases might dephosphorylate FTY720-P, we overexpressed the broad specificity lipid phosphatases LPP1–3, and the specific S1P phosphatases (SPP1 and 2) in HEK293 cells, and performed in vitro assays using lysates of transfected cells. Among LPPs, only LPP3 was able to dephosphorylate FTY720-P; among SPPs, only SPP1 showed activity against FTY720-P. On intact cells, LPP3 acted as an ecto-phosphatase or FTY720-P, thus representing the major phosphatase involved in the equilibrium between FTY720 and FTY720-P observed in vivo.
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