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TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22.
- Source :
-
Scientific reports [Sci Rep] 2017 May 18; Vol. 7 (1), pp. 2081. Date of Electronic Publication: 2017 May 18. - Publication Year :
- 2017
-
Abstract
- The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22). TRAF3 associated with Csk, promoting the dissociation of Csk from the plasma membrane. TRAF3 also associated with and regulated the TCR/CD28 induced localization of PTPN22. Loss of TRAF3 resulted in increased amounts of both Csk and PTPN22 in T cell membrane fractions and decreased association of PTPN22 with Csk. These findings identify a new role for T cell TRAF3 in promoting T cell activation, by regulating localization and functions of early TCR signaling inhibitors.
- Subjects :
- Animals
CSK Tyrosine-Protein Kinase
Cell Line, Tumor
Cell Membrane metabolism
Cells, Cultured
HEK293 Cells
Humans
Mice
Mice, Inbred C57BL
Protein Binding
Protein Transport
Protein Tyrosine Phosphatase, Non-Receptor Type 22 metabolism
T-Lymphocytes metabolism
TNF Receptor-Associated Factor 3 metabolism
src-Family Kinases metabolism
Receptors, Antigen, T-Cell metabolism
Signal Transduction
TNF Receptor-Associated Factor 3 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28522807
- Full Text :
- https://doi.org/10.1038/s41598-017-02280-4