Back to Search
Start Over
Phospho-SXXE/D Motif Mediated TNF Receptor 1-TRADD Death Domain Complex Formation for T Cell Activation and Migration.
- Source :
-
Journal of Immunology . 8/1/2011, Vol. 187 Issue 3, p1289-1297. 9p. - Publication Year :
- 2011
-
Abstract
- In TNF-treated cells, TNFR1, TNFR-associated death domain protein (TRADD), Fas-associated death domain protein, and receptor-interacting protein kinase proteins form the signaling complex via modular interaction within their C-terminal death domains. In this paper, we report that the death domain SXXE/D motifs (i.e., S381DHE motif of TNFR1-death domain as well as S215LKD and S296LAE motifs of TRADD-death domain) are phosphorylated, and this is required for stable TNFR1-TRADD complex formation and subsequent activation of NF-κB. Phospho-S215LKD and phospho-S296LAE motifs are also critical to TRADD for recruiting Fas-associated death domain protein and receptor-interacting protein kinase. I?B kinase β plays a critical role in TNFR1 phosphorylation of S381, which leads to subsequent T cell migration and accumulation. Consistently, we observed in inflammatory bowel disease specimens that TNFR1 was constitutively phosphorylated on S381 in those inflammatory T cells, which had accumulated in high numbers in the inflamed mucosa. Therefore, SXXE/D motifs found in the cytoplasmic domains of many TNFR family members and their adaptor proteins may serve to function as a specific interaction module for the α-helical death domain signal transduction. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TUMOR necrosis factors
*PROTEIN kinases
*T cells
*CELL death
*CELL migration
Subjects
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 187
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 66170269
- Full Text :
- https://doi.org/10.4049/jimmunol.1003399