Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B.

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.
Mesh Terms:
Amino Acid Sequence, Antigens, CD, Antigens, CD137, Blotting, Western, Cell Line, Electrophoresis, Polyacrylamide Gel, Genes, Reporter, Humans, Molecular Sequence Data, Mutation, NF-kappa B, Protein Binding, Protein-Serine-Threonine Kinases, Proteins, Receptors, Nerve Growth Factor, Receptors, Tumor Necrosis Factor, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Signal Transduction, T-Lymphocytes, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 3, Transfection
Biochem. Biophys. Res. Commun.
Date: Jan. 26, 1998
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