Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1).
Tumor necrosis factor-alpha (TNF), a major inflammatory cytokine, generates a wide variety of cellular responses via key cytoplasmic adaptor molecules named TNF receptor-associated factors (TRAFs). We report that TRAF2, TRAF5 and TRAF6 associate with apoptosis signal-regulating kinase 1 (ASK1), and a catalytically-inactive ASK1 mutant blocks stress-activated protein kinase (SAPK)/Jun NH2-terminal ... kinase (JNK) activation by these TRAFs. A truncated derivative of TRAF2, which inhibits SAPK activation by TNF, blocks TNF-induced ASK1 activation. Furthermore, protection from TNF-induced cell death conferred by an ASK1 mutant is dependent upon TRAF2. Hence, ASK1 is a common mediator of TRAF-regulated SAPK and apoptosis signaling, and the TRAF2 - ASK1 connection completes the signaling cascade from TNF to SAPK/JNK activation.
Mesh Terms:
Animals, Apoptosis, COS Cells, Cells, Cultured, Enzyme Activation, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinase 5, MAP Kinase Kinase Kinases, Mice, Mitogen-Activated Protein Kinases, Peptide Mapping, Proteins, Receptors, Tumor Necrosis Factor, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 5, TNF Receptor-Associated Factor 6, Tumor Necrosis Factor-alpha
Animals, Apoptosis, COS Cells, Cells, Cultured, Enzyme Activation, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinase 5, MAP Kinase Kinase Kinases, Mice, Mitogen-Activated Protein Kinases, Peptide Mapping, Proteins, Receptors, Tumor Necrosis Factor, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 5, TNF Receptor-Associated Factor 6, Tumor Necrosis Factor-alpha
Oncogene
Date: Oct. 14, 1999
PubMed ID: 10523862
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