FTY720-phosphate is dephosphorylated by lipid phosphate phosphatase 3.
FEBS Lett
; 581(16): 3063-8, 2007 Jun 26.
Article
en En
| MEDLINE
| ID: mdl-17555747
ABSTRACT
FTY720 is a novel immunomodulatory drug efficacious in the treatment of multiple sclerosis. The drug is converted in vivo to the monophosphate, FTY720-P, by sphingosine kinase 2. This conversion is incomplete, suggesting opposing actions of kinase and phosphatase activities. To address which of the known lipid phosphatases might dephosphorylate FTY720-P, we overexpressed the broad specificity lipid phosphatases LPP1-3, and the specific S1P phosphatases (SPP1 and 2) in HEK293 cells, and performed in vitro assays using lysates of transfected cells. Among LPPs, only LPP3 was able to dephosphorylate FTY720-P; among SPPs, only SPP1 showed activity against FTY720-P. On intact cells, LPP3 acted as an ecto-phosphatase or FTY720-P, thus representing the major phosphatase involved in the equilibrium between FTY720 and FTY720-P observed in vivo.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glicoles de Propileno
/
Esfingosina
/
Fosfatidato Fosfatasa
Límite:
Humans
Idioma:
En
Revista:
FEBS Lett
Año:
2007
Tipo del documento:
Article
País de afiliación:
Austria