RT info:eu-repo/semantics/article
T1 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
A1 Cianferoni, Antonella
A1 Massaad, Michel
A1 Feske, Stefan
A1 Fuente García, Miguel Ángel de la
A1 Gallego, María Dolores
A1 Ramesh, Narayanaswamy
A1 Geha, Raif S.
K1 Wiskott Aldrich, Síndrome
K1 Biología celular
AB Background: Proliferation and IL-2 production in response toT-cell receptor ligation are impaired in patients with Wiskott-Aldrich syndrome (WAS). The transcription factors nuclearfactor-kB (NF-kB), nuclear factor of activated T cells (NF-AT),and activating protein-1 (AP-1) play a critical role in IL-2 geneexpression.Objective: To investigate the mechanisms of impaired IL-2production after T-cell receptor ligation in T cells deficient inWAS protein (WASP).Methods: T cells from WASP2/2 mice were stimulated withanti-CD3 and anti-CD28. Nuclear NF-kB, NF-AT, and AP-1DNA-binding activity was examined by electroshift mobilityassay. NF-ATp dephosphorylation and nuclear localizationwere examined by Western blot and indirect immunofluorescence.Phosphorylation of the mitogen-activated proteinkinases Erk and Jnk, and of their nuclear substrates Elk-1 andc-Jun, was examined by Western blot. Expression of mRNA forIL-2 and the NF-kB–dependent gene A20 and of the AP-1components c-fos and c-Jun was examined by quantitativeRT-PCR.Results: Nuclear translocation and activity of NF-kB werenormal in T cells from WASP2/2 mice. In contrast, NF-ATpdephosphorylation and nuclear localization, nuclear AP-1binding activity, and expression of c-fos, but not c-Jun, were allimpaired. Phosphorylation of Jnk, c-Jun, and Erk were normal.However, nuclear translocation of phosphorylatedErk and phosphorylation of its nuclear substrate Elk1,which activates the c-fos promoter, were impaired.Conclusion: These results suggest that WASP is essential forNF-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-cellproliferation in WAS.
PB Elsevier
SN 0091-6749
YR 2005
FD 2005
LK http://uvadoc.uva.es/handle/10324/9843
UL http://uvadoc.uva.es/handle/10324/9843
LA eng
NO Journal of Allergy and Clinical Immunology, 2005 ;116(6):1364-71.
NO Producción Científica
DS UVaDOC
RD 25-abr-2024