Role of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) in distinct and overlapping CD40 and TNF receptor 2/CD120b-mediated B lymphocyte activation

Melissa E Munroe; Gail A Bishop

doi:10.1074/jbc.M410539200

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Role of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) in distinct and overlapping CD40 and TNF receptor 2/CD120b-mediated B lymphocyte activation

Journal article

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Peer reviewed

Role of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) in distinct and overlapping CD40 and TNF receptor 2/CD120b-mediated B lymphocyte activation

Melissa E Munroe and Gail A Bishop

The Journal of biological chemistry, Vol.279(51), pp.53222-53231

12/17/2004

DOI: 10.1074/jbc.M410539200

PMID: 15485859

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Abstract

Members of the tumor necrosis factor receptor (TNFR) family play a variety of roles in the regulation of lymphocyte activation. An important TNFR family member for B cell activation is CD40. CD40 signals stimulate B cell TNF-alpha secretion, which subsequently signals via TNFR2 (CD120b) to enhance B cell activation. Although the function of the pro-apoptotic and pro-inflammatory receptor TNFR1 (CD120a) has been the subject of much research, less is understood about the distinct contributions of CD120b to cell activation and how it stimulates downstream events. Members of the tumor necrosis factor receptor family bind various members of the cytoplasmic adapter protein family, the tumor necrosis factor receptor-associated factors (TRAFs), during signaling. Both CD40 and CD120b bind TNF receptor-associated factor 2 (TRAF2) upon ligand stimulation. Wild type and TRAF2-deficient B cells expressing CD40 or the hybrid molecule (human) CD40 (mouse)-CD120b were examined. CD40- and CD120b-mediated IgM secretion were partly TRAF2-dependent, but only CD40 required TRAF2 for c-Jun N-terminal kinase activation. CD40 and CD120b used primarily divergent mechanisms to activate NF-kappaB, exemplifying how TNFR family members can use diverse mechanisms to mediate similar downstream events.

Phosphorylation

Luciferases - metabolism

Antibodies - chemistry

Humans

Transcriptional Activation

Cytoplasm - metabolism

JNK Mitogen-Activated Protein Kinases - metabolism

NF-kappa B - metabolism

Immunoglobulin M - chemistry

Transcription Factor RelB

CD40 Antigens - biosynthesis

Mitogen-Activated Protein Kinase Kinases - metabolism

MAP Kinase Kinase 4

Transfection

Time Factors

Active Transport, Cell Nucleus

Antibodies, Monoclonal - chemistry

B-Lymphocytes - metabolism

Protein Structure, Tertiary

Proto-Oncogene Proteins - metabolism

Cell Line

Detergents - pharmacology

NF-kappa B p52 Subunit

Signal Transduction

Lymphocyte Activation

TNF Receptor-Associated Factor 2 - metabolism

Transcription Factors - metabolism

Adaptor Proteins, Signal Transducing

Animals

Receptors, Tumor Necrosis Factor, Type II - biosynthesis

Models, Biological

Protein Binding

Ligands

Trans-Activators - metabolism

Mice

Enzyme Activation

Kinetics

Apoptosis

Details

Title: Subtitle: Role of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) in distinct and overlapping CD40 and TNF receptor 2/CD120b-mediated B lymphocyte activation
Creators: Melissa E Munroe - Department of Microbiology, The University of Iowa and Veterans Affairs Medical Center, Iowa City, IA 52242, USA
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.279(51), pp.53222-53231
DOI: 10.1074/jbc.M410539200
PMID: 15485859
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: AI07343 / NIAID NIH HHS AI49993 / NIAID NIH HHS AI28847 / NIAID NIH HHS CA099997 / NCI NIH HHS AI07260 / NIAID NIH HHS
Language: English
Date published: 12/17/2004
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001218502771

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