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Receptor activator of NF‐κB recruits multiple TRAF family adaptors and activates c‐Jun N‐terminal kinase
Author(s) -
Kim Hong-Hee,
Lee Da Eun,
Shin Jin Na,
Lee Yong Soo,
Jeon Yoo Mi,
Chung Chae-Heon,
Ni Jian,
Kwon Byoung Se,
Lee Zang Hee
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01731-1
Subject(s) - activator (genetics) , microbiology and biotechnology , signal transduction , receptor , kinase , biology , nf κb , rank ligand , c jun , transcription factor , chemistry , biochemistry , gene , rankl
Receptor activator of NF‐κB (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‐κB 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.