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  • Title: Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B.
    Author: Jang IK, Lee ZH, Kim YJ, Kim SH, Kwon BS.
    Journal: Biochem Biophys Res Commun; 1998 Jan 26; 242(3):613-20. PubMed ID: 9464265.
    Abstract:
    Human 4-1BB (CD137), a member of the tumor necrosis factor receptor (TNFR) superfamily, costimulates T cell activation. No apparent intrinsic kinase activity is seen with 4-1BB, which suggests that 4-1BB-associated molecules may be involved in 4-1BB-mediated signal transduction. We found that tumor necrosis factor receptor-associated factor (TRAF) 1, TRAF2, and TRAF3, all interacted with the cytoplasmic domain of 4-1BB. Mutation analysis showed that TRAF1, TRAF2, and TRAF3 were associated with one of two runs of acidic residues found in the cytoplasmic domain of 4-1BB. In addition, 4-1BB cross-linking with TCR signal in Jurkat cells and overexpression of 4-1BB in 293 cells were able to induce activation of the nuclear factor-kappa B (NF-kappa B). 4-1BB-mediated NF-kappa B activation was inhibited by a dominant negative-TRAF2 or -NF-kappa B-inducing kinase (NIK). These data suggest that 4-1BB functions may be mediated by NF-kappa B activation, which requires a TRAF2/NIK pathway.
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