Document Detail

Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1).
MedLine Citation:
PMID:  10523862     Owner:  NLM     Status:  MEDLINE    
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.
K P Hoeflich; W C Yeh; Z Yao; T W Mak; J R Woodgett
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  18     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-11-19     Completed Date:  1999-11-19     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  5814-20     Citation Subset:  IM    
Department of Medical Biophysics, Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
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MeSH Terms
Apoptosis / physiology*
COS Cells
Cells, Cultured
Enzyme Activation
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase Kinase 5
MAP Kinase Kinase Kinases / biosynthesis,  genetics,  physiology*
Mitogen-Activated Protein Kinases / metabolism
Peptide Mapping
Proteins / metabolism*
Receptors, Tumor Necrosis Factor / metabolism*
Signal Transduction / physiology*
TNF Receptor-Associated Factor 2
TNF Receptor-Associated Factor 5
TNF Receptor-Associated Factor 6
Tumor Necrosis Factor-alpha
Reg. No./Substance:
0/Proteins; 0/Receptors, Tumor Necrosis Factor; 0/TNF Receptor-Associated Factor 2; 0/TNF Receptor-Associated Factor 5; 0/TNF Receptor-Associated Factor 6; 0/Tumor Necrosis Factor-alpha; EC Mitogen-Activated Protein Kinases; EC Protein Kinases; EC Kinase Kinase Kinase 5; EC Kinase Kinase Kinases; EC protein, mouse

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