Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling

Bruce S Hostager; Sokol A Haxhinasto; Sarah L Rowland; Gail A Bishop

doi:10.1074/jbc.M306708200

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Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling

Journal article

Open access

Peer reviewed

Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling

Bruce S Hostager, Sokol A Haxhinasto, Sarah L Rowland and Gail A Bishop

The Journal of biological chemistry, Vol.278(46), pp.45382-45390

11/14/2003

DOI: 10.1074/jbc.M306708200

PMID: 12958312

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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.

Up-Regulation

Humans

Insecta

NF-kappa B - metabolism

TNF Receptor-Associated Factor 2

TNF Receptor-Associated Factor 3

Immunoglobulin M - metabolism

CD40 Antigens - biosynthesis

Mitogen-Activated Protein Kinase Kinases - metabolism

MAP Kinase Kinase 4

Time Factors

Recombination, Genetic

JNK Mitogen-Activated Protein Kinases

B7-1 Antigen - biosynthesis

B-Lymphocytes - metabolism

Cell Line

Proteins - physiology

Signal Transduction

CD40 Ligand - biosynthesis

Plasmids - metabolism

Blotting, Western

TNF Receptor-Associated Factor 6

Animals

Proteins - metabolism

Mice

Models, Genetic

Genetic Vectors

Details

Title: Subtitle: Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling
Creators: Bruce S Hostager - Department of Pediatrics, Interdisciplinary Program in Immunology, University of Iowa, Iowa City 52242, USA
Sokol A Haxhinasto
Sarah L Rowland
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.278(46), pp.45382-45390
DOI: 10.1074/jbc.M306708200
PMID: 12958312
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: AI49993 / NIAID NIH HHS AI28847 / NIAID NIH HHS
Language: English
Date published: 11/14/2003
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984002395102771

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