PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes.

Détails

Ressource 1Télécharger: BIB_C675F24FFBA8.P001.pdf (3776.33 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_C675F24FFBA8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes.
Périodique
PLoS One
Auteur(s)
Thuille N., Wachowicz K., Hermann-Kleiter N., Kaminski S., Fresser F., Lutz-Nicoladoni C., Leitges M., Thome M., Massoumi R., Baier G.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2013
Volume
8
Numéro
1
Pages
e53709
Langue
anglais
Résumé
In T cells PKCθ mediates the activation of critical signals downstream of TCR/CD28 stimulation. We investigated the molecular mechanisms by which PKCθ regulates NFκB transactivation by examining PKCθ/β single and double knockout mice and observed a redundant involvement of PKCθ and PKCβ in this signaling pathway. Mechanistically, we define a PKCθ-CYLD protein complex and an interaction between the positive PKCθ/β and the negative CYLD signaling pathways that both converge at the level of TAK1/IKK/I-κBα/NFκB and NFAT transactivation. In Jurkat leukemic T cells, CYLD is endoproteolytically processed in the initial minutes of stimulation by the paracaspase MALT1 in a PKC-dependent fashion, which is required for robust IL-2 transcription. However, in primary T cells, CYLD processing occurs with different kinetics and an altered dependence on PKC. The formation of a direct PKCθ/CYLD complex appears to regulate the short-term spatial distribution of CYLD, subsequently affecting NFκB and NFAT repressional activity of CYLD prior to its MALT1-dependent inactivation. Taken together, our study establishes CYLD as a new and critical PKCθ interactor in T cells and reveals that antagonistic PKCθ/β-CYLD crosstalk is crucial for the adjustment of immune thresholds in primary mouse CD3(+) T cells.
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/03/2013 11:27
Dernière modification de la notice
09/05/2019 1:03
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