4-1BB 신호전달경로에 관여하는 Tumor Necrosis Factor Receptor-Associated Factor-2(TRAF-2)에 관한 연구
A Study on Tumor Necrosis Factor Receptor-Associated Factor-2(TRAF-2) Involved in 4-1BB Signal Transduction
이장희, 조재오, 김창목,
소속 상세정보
이장희 ( ) - 조선대학교 치과대학 미생물학,
조재오 ( ) - 조선대학교 치과대학 구강병리학교실
김창목 ( ) - 조선대학교 치과대학 미생물학,
KMID : 0829219980220010001
Abstract
Human 4-lBB(CD137),a member of the tumor necrosis factor receptor(TNFR)family,plays an important role in Tcell activation as a costimulatory molecule. 4-1BB appears to have no intrinsic kinase activity, suggesting that 4-IBB associated molecules may be involved in 4-lBB-mediated signal transduction. To characterize the early transmembrane signaling event taking place after 4-1IBB stimulation, the yeast two-hybrid system was used to identify such signaling molecutes. It was shown that tumor necrosis factor receptor-associated factor (TRAF)-2 interacteracted with the cytoplasmic domain of 4-1IBB.
The specific interaction between 4-1BB and TRAF2 was proved by in vitro binding assay using CST fusion protein and in vivo binding assay. Although other TRAF members were not positively identified in the yeast two-hybrid screening, it was examined whether othe TRAF members, TRAF1 and TRAf3 interacted to 4-1BB or not. It was shown that TRAF1 and TRAF3 directly interacted with 4-1BB. Specifically, mutation analyses showed that TRAF2 bound to either one of two motifs consisting of consequtive acidic amino acid residues found in the C-terminus of 4-lBB. These data suggest that 4-lBB faction requires THAF2-mediated signals.
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