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ASK1 is essential for JNK/SAPK activation by TRAF2
H Nishitoh1, M Saitoh, Y Mochida
1Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Molecular Cell
|October 17, 1998
Summary
Tumor necrosis factor (TNF) activates c-jun N-terminal kinase (JNK) through TNF receptor-associated factor 2 (TRAF2). Apoptosis signal-regulating kinase 1 (ASK1) mediates this TRAF2-induced JNK activation.
Area of Science:
- Cellular signaling pathways
- Molecular biology
- Immunology
Background:
- Tumor necrosis factor (TNF) signaling activates c-jun N-terminal kinase (JNK).
- TNF receptor-associated factor 2 (TRAF2) is essential for TNF-induced JNK activation.
- The role of apoptosis signal-regulating kinase 1 (ASK1) in this pathway is not fully elucidated.
Purpose of the Study:
- To investigate the role of ASK1 in TNF-induced JNK activation.
- To determine the interaction between ASK1 and TRAF family members.
- To elucidate the mechanism by which TRAF2 mediates JNK activation.
Main Methods:
- Overexpression of TRAF family members and ASK1 mutants.
- Analysis of JNK activation using kinase assays.
- Co-immunoprecipitation to study protein interactions.
- Dominant-negative inhibition assays.
Main Results:
- ASK1 interacts with TRAF2, TRAF5, and TRAF6.
- TRAF2 overexpression activates ASK1.
- A dominant-negative ASK1 mutant inhibits TNF- and TRAF2-induced JNK activation.
- ASK1 associates with TRAF2 in a TNF-dependent manner in mammalian cells.
Conclusions:
- ASK1 is a key mediator of TRAF2-induced JNK activation.
- The ASK1-TRAF2 interaction is crucial for TNF signaling.
- This study clarifies a critical step in the TNF-JNK signaling cascade.