Journal
FEBS LETTERS
Volume 554, Issue 1-2, Pages 189-193Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(03)01168-2
Keywords
FTY720; sphingosine kinase; sphingosine; sphingosine-1-phosphate; phosphorylation
Funding
- NCI NIH HHS [CA61774] Funding Source: Medline
- NIAID NIH HHS [AI50094] Funding Source: Medline
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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. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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