[HTML][HTML] Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability

T Sanchez, T Estrada-Hernandez, JH Paik… - Journal of Biological …, 2003 - ASBMB
FTY720, a potent immunosuppressive agent, is phosphorylated in vivo into FTY720-P, a
high affinity agonist for sphingosine 1-phosphate (S1P) receptors. The effects of FTY720 on
vascular cells, a major target of S1P action, have not been addressed. We now report the
metabolic activation of FTY720 by sphingosine kinase-2 and potent activation of vascular
endothelial cell functions in vitro and in vivo by phosphorylated FTY720 (FTY720-P).
Incubation of endothelial cells with FTY720 resulted in phosphorylation by sphingosine …