Journal article
Differential TRAF3 utilization by a variant human CD40 receptor with enhanced signaling
The Journal of immunology (1950), Vol.185(11), pp.6555-6562
12/01/2010
DOI: 10.4049/jimmunol.1000135
PMCID: PMC3040440
PMID: 21041727
Abstract
CD40 is required for T-dependent humoral immunity, but can also contribute to the pathogenesis of autoimmunity and B cell malignancy. The TNF receptor associated factor (TRAF)2 and TRAF6 adaptor proteins are positive regulators of CD40 signaling required to activate downstream kinase cascades and transcription factors. In contrast, TRAF3 can serve as a negative regulator of CD40 signaling, and CD40 signals are amplified in TRAF3
−/−
B cells. We previously reported a gain-of-function polymorphism of the human CD40 receptor, hCD40-P227A, which signals in an amplified manner to B lymphocytes. Here, we show that hCD40-P227A binds more TRAF3 and TRAF5, as well as certain associated proteins, than Wt-CD40. Studies in TRAF-deficient B cell lines revealed that hCD40-P227A uses TRAF3 as a positive rather than negative regulator. Although located outside of any known TRAF binding sites, the P227A polymorphism can alter TRAF binding and dramatically changes the role played by TRAF3 in CD40 signaling.
Details
- Title: Subtitle
- Differential TRAF3 utilization by a variant human CD40 receptor with enhanced signaling
- Creators
- Anna L Peters - VA Medical Center, Iowa City, IAGail A Bishop - VA Medical Center, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.185(11), pp.6555-6562
- DOI
- 10.4049/jimmunol.1000135
- PMID
- 21041727
- PMCID
- PMC3040440
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 12/01/2010
- Academic Unit
- Microbiology and Immunology; President
- Record Identifier
- 9984001139102771
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