NRAMP-1 expression modulates protein-tyrosine phosphatase activity in macrophages: impact on host cell signaling and functions.
J Biol Chem
; 282(50): 36190-8, 2007 Dec 14.
Article
en En
| MEDLINE
| ID: mdl-17942403
NRAMP-1 (natural resistance-associated macrophage protein-1) has been associated with innate resistance to unrelated intracellular pathogen infections, up-regulation of proinflammatory phagocyte functions, and susceptibility to autoimmune diseases. It is still unclear how the divalent cation transport function of NRAMP-1 accounts for the associated pleiotropic effects. In this study, we evaluated the impact of murine macrophage NRAMP-1 expression on the activity of protein-tyrosine phosphatases (PTPs) as an upstream event contributing to the NRAMP-1 regulation of signal transduction and control of effector macrophage functions. Functional expression of NRAMP-1 results in lower macrophage PTP activity and increased protein phosphorylation. Decreased PTP activity is not a result of changes in protein expression but rather a reversible regulatory mechanism involving the interaction with NRAMP-1 metal substrates. In the context of intracellular infections, NRAMP-1 expression prevents full macrophage PTP induction by Leishmania infection, correlating with higher nitric oxide production and lower parasite survival. We suggest that NRAMP-1 divalent cation transport leads to transient inhibition of PTPs via direct PTP-metal interaction and/or by reactive oxygen species-dependent PTP oxidation, consequently promoting positive signal transduction, as a backbone for the induction of proinflammatory phagocyte functions.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leishmania donovani
/
Transducción de Señal
/
Proteínas Tirosina Fosfatasas
/
Proteínas de Transporte de Catión
/
Leishmaniasis Visceral
/
Macrófagos
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2007
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Estados Unidos