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Título
Defective nuclear translocation of nuclear factor of activated T cells and extracellular signal-regulated kinase underlies deficient IL-2 gene expression in Wiskott-Aldrich syndrome
Autor
Año del Documento
2005
Editorial
Elsevier
Descripción
Producción Científica
Documento Fuente
Journal of Allergy and Clinical Immunology, 2005 ;116(6):1364-71.
Resumo
Background: Proliferation and IL-2 production in response to
T-cell receptor ligation are impaired in patients with Wiskott-
Aldrich syndrome (WAS). The transcription factors nuclear
factor-kB (NF-kB), nuclear factor of activated T cells (NF-AT),
and activating protein-1 (AP-1) play a critical role in IL-2 gene
expression.
Objective: To investigate the mechanisms of impaired IL-2
production after T-cell receptor ligation in T cells deficient in
WAS protein (WASP).
Methods: T cells from WASP2/2 mice were stimulated with
anti-CD3 and anti-CD28. Nuclear NF-kB, NF-AT, and AP-1
DNA-binding activity was examined by electroshift mobility
assay. NF-ATp dephosphorylation and nuclear localization
were examined by Western blot and indirect immunofluorescence.
Phosphorylation of the mitogen-activated protein
kinases Erk and Jnk, and of their nuclear substrates Elk-1 and
c-Jun, was examined by Western blot. Expression of mRNA for
IL-2 and the NF-kB–dependent gene A20 and of the AP-1
components c-fos and c-Jun was examined by quantitative
RT-PCR.
Results: Nuclear translocation and activity of NF-kB were
normal in T cells from WASP2/2 mice. In contrast, NF-ATp
dephosphorylation and nuclear localization, nuclear AP-1
binding activity, and expression of c-fos, but not c-Jun, were all
impaired. Phosphorylation of Jnk, c-Jun, and Erk were normal.
However, nuclear translocation of phosphorylated
Erk and phosphorylation of its nuclear substrate Elk1,
which activates the c-fos promoter, were impaired.
Conclusion: These results suggest that WASP is essential for
NF-ATp activation, and for nuclear translocation of p-Erk,
Elk1 phosphorylation, and c-fos gene expression in T cells.
These defects underlie defective IL-2 expression and T-cell
proliferation in WAS.
Materias (normalizadas)
Wiskott Aldrich, Síndrome
Biología celular
ISSN
0091-6749
Revisión por pares
SI
Idioma
eng
Derechos
openAccess
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