IκB kinase α phosphorylation of TRAF4 downregulates innate immune signaling.
Mol Cell Biol
; 32(13): 2479-89, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22547678
ABSTRACT
Despite their homology, IκB kinase α (IKKα) and IKKß have divergent roles in NF-κB signaling. IKKß strongly activates NF-κB while IKKα can downregulate NF-κB under certain circumstances. Given this, identifying independent substrates for these kinases could help delineate their divergent roles. Peptide substrate array technology followed by bioinformatic screening identified TRAF4 as a substrate for IKKα. Like IKKα, TRAF4 is atypical within its family because it is the only TRAF family member to negatively regulate innate immune signaling. IKKα's phosphorylation of serine-426 on TRAF4 was required for this negative regulation. Binding to the Crohn's disease susceptibility protein, NOD2, is required for TRAF4 phosphorylation and subsequent inhibition of NOD2 signaling. Structurally, serine-426 resides within an exaggerated ß-bulge in TRAF4 that is not present in the other TRAF proteins, and phosphorylation of this site provides a structural basis for the atypical function of TRAF4 and its atypical role in NOD2 signaling.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinase I-kappa B
/
Fator 4 Associado a Receptor de TNF
/
Imunidade Inata
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article