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  • Title: The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2.
    Author: Paugh SW, Payne SG, Barbour SE, Milstien S, Spiegel S.
    Journal: FEBS Lett; 2003 Nov 06; 554(1-2):189-93. PubMed ID: 14596938.
    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.
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