The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2

FEBS Letters

Paugh, Steven W.²  Payne, Shawn G.²  Barbour, Suzanne E.²  Milstien, Sheldon¹  Spiegel, Sarah² 

[1] Laboratory of Cellular and Molecular Regulation, NIMH, NIH, Bethesda, MD 20892, USA;Department of Biochemistry, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA

关键词: FTY720;    Sphingosine kinase;    Sphingosine;    Sphingosine-1-phosphate;    Phosphorylation;    BSA;    bovine serum albumin;    S1P;    sphingosine-1-phosphate;    SphK1;    sphingosine kinase type 1;    SphK2;    sphingosine kinase type 2;    TLC;    thin layer chromatography;   

DOI  :  10.1016/S0014-5793(03)01168-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The potent immunosuppressive drug FTY720, a sphingosine analog, induces redistribution of lymphocytes from circulation to secondary lymphoid tissues. FTY720 is phosphorylated in vivo and functions as an agonist for four G-protein-coupled sphingosine-1-phosphate receptors. The identity of the kinase that phosphorylates FTY720 is still not known. Here we report that although both sphingosine kinase type 1 (SphK1) and type 2 (SphK2) can phosphorylate FTY720 with low efficiency, SphK2 is much more effective than SphK1. FTY720 inhibited phosphorylation of sphingosine catalyzed by SphK2 to a greater extent than it inhibits SphK1. Thus, SphK2 may be the relevant enzyme that is responsible for in vivo phosphorylation of FTY720.

【 授权许可】

Unknown