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TNF-related weak inducer of apoptosis receptor, a TNF receptor superfamily member, activates NF-κB through TNF receptor-associated factors
- TNF-related weak inducer of apoptosis receptor, a TNF receptor superfamily member, activates NF-κB through TNF receptor-associated factors
- Han S.; Yoon K.; Lee K.; Kim K.; Jang H.; Lee N.K.; Hwang K.; Lee S.Y.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Biochemical and Biophysical Research Communications
- vol. 305, no. 4, pp. 789 - 796
- SCI; SCIE; SCOPUS
- TNF-related weak inducer of apoptosis (TWEAK) is a member of the TNF ligand family that induces angiogenesis in vivo. The TWEAK receptor (TweakR) is a recently identified member of the TNF receptor (TNFR) superfamily and is expressed on smooth muscle cells (SMCs) and endothelial cells (ECs). In this report we identify the TNF receptor-associated factor (TRAF) family of signal transducers as important components of TweakR-mediated NF-κB activation. Coimmunoprecipitation experiments suggested potential interactions between the cytoplasmic tail of TweakR with TRAFs 1, 2, 3, and 5. Dominant negative forms of TRAF2 and TRAF5 substantially inhibited TweakR-mediated NF-κB activation, suggesting a role of TRAFs in regulating smooth muscle and endothelial cell function. Using alanine-scanning analysis, we defined a TRAF-binding motif, PIEET, in TweakR that mediates TRAF binding and NF-κB activation. Furthermore, TweakR mutations within the TRAF-binding motif abolished TweakR-stimulated SMC migration, revealing a role for TRAFs in TweakR-induced activation events. © 2003 Elsevier Science (USA). All rights reserved.
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