The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2.

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Paugh SW, Payne SG, Barbour SE, Milstien S, Spiegel S

The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2.

FEBS Lett. 2003 Nov 6;554(1-2):189-93. doi: 10.1016/s0014-5793(03)01168-2.

PubMed ID

14596938 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Fingolimod	Sphingosine kinase 1	Protein	Humans	Unknown	Substrate Inhibitor	Details