Receptor activator of NF-kappaB recruits multiple TRAF family adaptors and activates c-Jun N-terminal kinase.
Receptor activator of NF-kappaB (RANK) is a recently cloned member of the tumor necrosis factor receptor (TNFR) superfamily, and its function has been implicated in osteoclast differentiation and dendritic cell survival. Many of the TNFR family receptors recruit various members of the TNF receptor-associated factor (TRAF) family for transduction of ... their signals to NF-kappaB and c-Jun N-terminal kinase. In this study, the involvement of TRAF family members and the activation of the JNK pathway in signal transduction by RANK were investigated. TRAF1, 2, 3, 5, and 6 were found to bind RANK in vitro. Association of RANK with each of these TRAF proteins was also detected in vivo. Expression of RANK in cultured cells also induced the activation of JNK, which was blocked by a dominant-negative form of JNK. Furthermore, by employing various C-terminal deletion mutants of RANK, the regions responsible for TRAF interaction and JNK activation were identified. TRAF5 was determined to bind to the C-terminal 11 amino acids and the other TRAF members to a region N-terminal to the TRAF5 binding site. The domain responsible for JNK activation was localized to the same region where TRAF1, 2, 3, and 6 bound, which suggests that these TRAF molecules might mediate the RANK-induced JNK activation.
Mesh Terms:
Amino Acid Sequence, Binding Sites, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Cell Line, Enzyme Activation, Hela Cells, Humans, JNK Mitogen-Activated Protein Kinases, Membrane Glycoproteins, Mitogen-Activated Protein Kinases, Precipitin Tests, Protein Binding, Proteins, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Receptors, Tumor Necrosis Factor, Recombinant Fusion Proteins, Sequence Deletion, Signal Transduction, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 3, TNF Receptor-Associated Factor 5, TNF Receptor-Associated Factor 6, Transfection
Amino Acid Sequence, Binding Sites, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Cell Line, Enzyme Activation, Hela Cells, Humans, JNK Mitogen-Activated Protein Kinases, Membrane Glycoproteins, Mitogen-Activated Protein Kinases, Precipitin Tests, Protein Binding, Proteins, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Receptors, Tumor Necrosis Factor, Recombinant Fusion Proteins, Sequence Deletion, Signal Transduction, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 3, TNF Receptor-Associated Factor 5, TNF Receptor-Associated Factor 6, Transfection
FEBS Lett.
Date: Jan. 29, 1999
PubMed ID: 10025951
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