TRAF1 phosphorylation on Serine 139 modulates NF-κB activity downstream of 4-1BB in T cells.
Biochem Biophys Res Commun
; 432(1): 129-34, 2013 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-23376065
ABSTRACT
The Tumour Necrosis Factor (TNF) Receptor-associated factor-1 (TRAF1) adaptor protein is a key component in initiating intracellular signalling pathways downstream of TNF receptors (TNFR). More importantly, TRAF1 has a pattern of expression restricted primarily to lymphoid cells and plays an important role in lymphocyte survival. TRAF1 has been shown to be phosphorylated on Serine 139, consequently inhibiting NF-κB activation downstream of TNFR2 when expressed in HeLa cells. We have previously demonstrated that TRAF1 cooperates with the TNFR family member 4-1BB to mediate signalling in T cells. However, the impact of TRAF1 phosphorylation on events downstream of 4-1BB in T cells remained to be defined. Using a proteomics approach we demonstrate that TANK-binding kinase 1 (TBK1) preferentially associates with the TRAF1 Serine 139 to Alanine (S139A) mutant. TBK1 is a kinase that functions upstream of NIK and IKK in the activation of the NF-κB pathway. When TRAF1-deficient CD8 T cells were reconstituted with the TRAF1 S139A mutant, we observed more sustained levels of IκBα degradation in response to 4-1BB stimulation in contrast to cells expressing either TRAF1 wild-type or TRAF1 S139D phospho-mimetic mutant. Together, these findings define the importance of the basal phosphorylation state of the TRAF1 Serine 139 residue in coordinating signalling events downstream of 4-1BB in primary T cells.
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Bases de dados:
MEDLINE
Assunto principal:
Linfócitos T
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NF-kappa B
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Fator 1 Associado a Receptor de TNF
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Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2013
Tipo de documento:
Article