| First Author | Oussa NA | Year | 2013 |
| Journal | Biochem Biophys Res Commun | Volume | 432 |
| Issue | 1 | Pages | 129-34 |
| PubMed ID | 23376065 | Mgi Jnum | J:198056 |
| Mgi Id | MGI:5495345 | Doi | 10.1016/j.bbrc.2013.01.073 |
| Citation | Oussa NA, et al. (2013) TRAF1 phosphorylation on Serine 139 modulates NF-kappaB activity downstream of 4-1BB in T cells. Biochem Biophys Res Commun 432(1):129-34 |
| abstractText | 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-kappaB 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-kappaB pathway. When TRAF1-deficient CD8 T cells were reconstituted with the TRAF1 S139A mutant, we observed more sustained levels of IkappaBalpha 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. |
