TNF-related weak inducer of apoptosis receptor, a TNF receptor superfamily member, activates NF-kappa B through TNF receptor-associated factors.
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-kappa B 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-kappa B 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-kappa B activation. Furthermore, TweakR mutations within the TRAF-binding motif abolished TweakR-stimulated SMC migration, revealing a role for TRAFs in TweakR-induced activation events.
Han
Songyi
S
Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, 11-1 Daehyun-dong, Seoul 120-750, Republic of Korea.
Yoon
Kwiyeom
K
Lee
Kyunghye
K
Kim
Kyunghee
K
Jang
Hyunduk
H
Lee
Na Kyung
NK
Hwang
Kichul
K
Young Lee
Soo
S
D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002465:Cell Movement; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000502:physiology; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2; D048015:TNF Receptor-Associated Factor 5; D000074050:TWEAK Receptor; D015533:Transcriptional Activation
D016328:NF-kappa B; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047992:TNF Receptor-Associated Factor 2; D048015:TNF Receptor-Associated Factor 5; D000074050:TWEAK Receptor