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.
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.
Department of Microbiology, The University of Iowa and Veterans Affairs Medical Center, Iowa City, IA 52242, USA.
Melissa E
ME
Munroe
Gail A
GA
Bishop
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000906:Antibodies / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000096:biosynthesis*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007075:Immunoglobulin M / Q000737:chemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D008213:Lymphocyte Activation; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D052003:NF-kappa B p52 Subunit; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000096:biosynthesis*; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D003902:Detergents; D007075:Immunoglobulin M; D008024:Ligands; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; C504649:PSIP1 protein, human; D011518:Proto-Oncogene Proteins; C504650:Psip1 protein, mouse; C497593:RELB protein, human; D047889:Receptors, Tumor Necrosis Factor, Type II; C497594:Relb protein, mouse; D047992:TNF Receptor-Associated Factor 2; D015534:Trans-Activators; D014157:Transcription Factors; D051841:Transcription Factor RelB; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases