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PMID:12958312

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Citation

Hostager, BS, Haxhinasto, SA, Rowland, SL and Bishop, GA (2003) Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling. J. Biol. Chem. 278:45382-90

Abstract

CD40 function is initiated by tumor necrosis factor (TNF) receptor-associated factor (TRAF) adapter proteins, which play important roles in signaling by numerous receptors. Characterizing roles of individual TRAFs has been hampered by limitations of available experimental models and the poor viability of most TRAF-deficient mice. Here, B cell lines made deficient in TRAF2 using a novel homologous recombination system reveal new roles for TRAF2. We demonstrate that TRAF2 participates in synergy between CD40 and B cell antigen receptor signals, and in CD40-mediated, TNF-dependent IgM production. We also find that TRAF2 participates in the degradation of TRAF3 associated with CD40 signaling, a role that may limit inhibitory actions of TRAF3. Finally, we show that TRAF2 and TRAF6 have overlapping functions in CD40-mediated NF-kappaB activation and CD80 up-regulation. These findings demonstrate previously unappreciated roles for TRAF2 in signaling by TNF receptor family members, using an approach that facilitates the analysis of genes critical to the viability of whole organisms.

Links

PubMed Online version:10.1074/jbc.M306708200

Keywords

Animals; Antigens, CD40/biosynthesis; Antigens, CD80/biosynthesis; B-Lymphocytes/metabolism; Blotting, Western; CD40 Ligand/biosynthesis; Cell Line; Genetic Vectors; Humans; Immunoglobulin M/metabolism; Insects; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Mice; Mitogen-Activated Protein Kinase Kinases/metabolism; Models, Genetic; NF-kappa B/metabolism; Plasmids/metabolism; Proteins/metabolism; Proteins/physiology; Recombination, Genetic; Signal Transduction; TNF Receptor-Associated Factor 2; TNF Receptor-Associated Factor 3; TNF Receptor-Associated Factor 6; Time Factors; Up-Regulation

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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