NDLI: RANK-mediated amplification of TRAF6 signaling leads to NFATc1 induction during osteoclastogenesis

Content Provider	PubMed Central
Author	Gohda, Jin Akiyama, Toru Koga, Takako Takayanagi, Hiroshi Tanaka, Sakae Inoue, Jun-ichiro
Copyright Year	2005
Abstract	RANK and CD40 activate NF-κB and MAPKs to similar levels via TRAF6. Even though overexpression of TRAF6 results in osteoclast formation, RANK but not CD40 promotes osteoclastogenesis. To understand the molecular basis for RANK-specific activity in osteoclastogenesis, we created an osteoclast formation system driven by anti-human CD40 antibody-mediated stimulation of a chimeric receptor, h40/mRK, which consists of the extracellular domain of human CD40 and the transmembrane and cytoplasmic domains of mouse RANK. By introducing mutations into three TRAF6-binding sites of RANK, we found that h40/mRK with a single TRAF6-binding site efficiently induced Ca2+ oscillation and expression of NFATc1, a master switch in osteoclastogenesis, whereas CD40 carrying a single TRAF6-binding site did not. However, expression of CD40 that was approximately 100 times greater than that of h40/mRK resulted in osteoclast formation, indicating that the RANK–TRAF6 signal is more potent than the CD40–TRAF6 signal in terms of NFATc1 activation and osteoclastogenesis. These results suggest that RANK may harbor a specific domain that amplifies TRAF6 signaling.
Related Links	http://dx.doi.org/10.1038/sj.emboj.7600564
Ending Page	799
Page Count	10
Starting Page	790
File Format	PDF
ISSN	02614189
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	4
Volume Number	24
Language	English
Publisher Date	2005-01-01
Access Restriction	Open
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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