TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40.
TNF receptor-associated factor (TRAF) proteins are candidate signal transducers that associate with the cytoplasmic domains of members of the tumor necrosis factor (TNF) receptor superfamily. The role of TRAFs in the TNF-R2 and CD40 signal transduction pathways, which result in the activation of transcription factor NF-kappa B, was investigated. Overexpression of TRAF2, but not TRAF1 or TRAF3, was sufficient to induce NF-kappa B activation. A truncated derivative of TRAF2 lacking an amino-terminal RING finger domain was a dominant-negative inhibitor of NF-kappa B activation mediated by TNF-R2 and CD40. Thus, TRAF2 is a common mediator of TNF-R2 and CD40 signaling.
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Molecular Biology Department, Tularik, Inc., South San Francisco, CA 94080, USA.
Sarma
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Dixit
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Goeddel
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D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D019013:CD40 Antigens; D002460:Cell Line; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2; D014162:Transfection
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D016328:NF-kappa B; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D047992:TNF Receptor-Associated Factor 2