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Chinese Medical Sciences Journal ; (4): 1-12, 2010.
Article Dans Anglais | WPRIM | ID: wpr-299467

Résumé

<p><b>OBJECTIVE</b>To investigate the role of TNF receptor-associated factor 2 (TRAF-2) and TRAF6 in CD40-induced nuclear factor-kappaB (NF-kappaB) signaling pathway and whether CD40 signaling requires TRAF2.</p><p><b>METHODS</b>Human B cell lines were transfected with plasmids expressing wild type TRAF2 or dominant negative TRAF2, TRAF2-shRNA, or TRAF6-shRNA. The activation of NF-kappaB was detected by Western blot, kinase assay, transfactor enzyme-linked immunosorbent assay (ELISA), and fluorescence resonance energy transfer (FRET). Analysis of the role of TRAF-2 and TRAF-6 in CD40-mediated NF-kappaB activity was examined following stimulation with recombinant CD154.</p><p><b>RESULTS</b>TRAF2 induced activity of IkappaB-kinases (IKKalpha, IKKi/epsilon), phosphorylation of IkappaBalpha, as well as nuclear translocation and phosphorylation of p65/RelA. In contrast, TRAF6 strongly induced NF-kappaB activation and nuclear translocation of p65 as well as p50 and c-Rel. Engagement of CD154-induced nuclear translocation of p65 was inhibited by a TRAF6-shRNA, but conversely was enhanced by a TRAF2-shRNA. Examination of direct interactions between CD40 and TRAFs by FRET documented that both TRAF2 and TRAF6 directly interacted with CD40. However, the two TRAFs competed for CD40 binding.</p><p><b>CONCLUSIONS</b>These results indicate that TRAF2 can signal in human B cells, but it is not essential for CD40-mediated NF-kappaB activation. Moreover, TRAF2 can compete with TRAF6 for CD40 binding, and thereby limit the capacity of CD40 engagement to induce NF-kappaB activation.</p>


Sujets)
Animaux , Humains , Lymphocytes B , Biologie cellulaire , Physiologie , Antigènes CD40 , Métabolisme , Lignée cellulaire , Extracellular Signal-Regulated MAP Kinases , Métabolisme , Transfert d'énergie par résonance de fluorescence , I-kappa B Kinase , Métabolisme , Facteur de transcription NF-kappa B , Génétique , Métabolisme , Protéines proto-oncogènes c-fos , Métabolisme , Transduction du signal , Physiologie , Facteur-2 associé aux récepteurs de TNF , Génétique , Métabolisme , Facteur-6 associé aux récepteurs de TNF , Génétique , Métabolisme , Facteur de transcription RelA , Métabolisme , p38 Mitogen-Activated Protein Kinases , Métabolisme
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