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- W4313359621 abstract "Abstract TRAF3 is an adaptor protein with diverse cell type-specific functions that plays an important role in T cell biology. T cell conditional TRAF3−/− mice, despite normal numbers of T cells, have poor responses to immunization and infection. Further investigation revealed that early events in T cell receptor (TCR) signaling are defective in TRAF3-deficient T cells. Examining the basis of this defect, we recently reported that TRAF3 normally inhibits localization of the negative regulators Csk and PTPN22 to the TCR membrane complex. We now wish to understand how TRAF3 is recruited to this complex. TRAF3 associates with the TCR-CD28 complex upon stimulation; engagement of both the TCR and CD28 is required for TRAF3 recruitment. We hypothesize that TRAF3 associates with the TCR complex either indirectly, by binding to other CD28-associated adaptor proteins, or directly, by binding to motifs in the cytoplasmic tail of CD28. Results of preliminary experiments suggest that the TRAF3 TRAF-C domain associates with Linker of Activated T cells (LAT), but not with the LAT-binding adaptor protein Gads. We are currently investigating the structural requirements for the association of TRAF3 with CD28, the adaptor protein Grb2, and other TCR signaling proteins, to determine how TRAF3 is recruited to the TCR complex. Based upon our previous finding that TRAF3 enhances TCR signaling by inhibiting the localization of negative regulatory proteins associated with the TCR, as well as our preliminary data indicating that TRAF3 interacts with members of the LAT complex, we are also investigating the interactions between TRAF3 and negative regulatory proteins associated with the LAT complex." @default.
- W4313359621 created "2023-01-06" @default.
- W4313359621 creator A5027957892 @default.
- W4313359621 creator A5057604637 @default.
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- W4313359621 date "2018-05-01" @default.
- W4313359621 modified "2023-09-28" @default.
- W4313359621 title "TRAF3-mediated regulation of the T cell receptor complex" @default.
- W4313359621 doi "https://doi.org/10.4049/jimmunol.200.supp.112.1" @default.
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