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IκB kinase α phosphorylation of TRAF4 downregulates innate immune signaling.
Marinis, Jill M; Hutti, Jessica E; Homer, Craig R; Cobb, Brian A; Cantley, Lewis C; McDonald, Christine; Abbott, Derek W.
Afiliação
  • Marinis JM; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Mol Cell Biol ; 32(13): 2479-89, 2012 Jul.
Article em En | MEDLINE | ID: mdl-22547678
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional 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 Revista: Mol Cell Biol Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional 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 Revista: Mol Cell Biol Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos