ASK1 is essential for JNK/SAPK activation by TRAF2.
Tumor necrosis factor (TNF)-induced activation of the c-jun N-terminal kinase (JNK, also known as SAPK; stress-activated protein kinase) requires TNF receptor-associated factor 2 (TRAF2). The apoptosis signal-regulating kinase 1 (ASK1) is activated by TNF and stimulates JNK activation. Here we show that ASK1 interacts with members of the TRAF family ... and is activated by TRAF2, TRAF5, and TRAF6 overexpression. A truncated derivative of TRAF2, which inhibits JNK activation by TNF, blocks TNF-induced ASK1 activation. A catalytically inactive mutant of ASK1 is a dominant-negative inhibitor of TNF- and TRAF2-induced JNK activation. In untransfected mammalian cells, ASK1 rapidly associates with TRAF2 in a TNF-dependent manner. Thus, ASK1 is a mediator of TRAF2-induced JNK activation.
Mesh Terms:
Animals, Apoptosis, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Enzyme Activation, Humans, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinases, Mammals, Mitogen-Activated Protein Kinases, Protein-Serine-Threonine Kinases, Proteins, Receptors, Tumor Necrosis Factor, Recombinant Proteins, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 5, TNF Receptor-Associated Factor 6, Transfection
Animals, Apoptosis, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Enzyme Activation, Humans, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinases, Mammals, Mitogen-Activated Protein Kinases, Protein-Serine-Threonine Kinases, Proteins, Receptors, Tumor Necrosis Factor, Recombinant Proteins, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 5, TNF Receptor-Associated Factor 6, Transfection
Mol. Cell
Date: Sep. 01, 1998
PubMed ID: 9774977
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