HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Taguchi, Y. Articles by Inoue, J.-i. PubMed Articles by Taguchi, Y. Articles by Inoue, J.-i.

¹ Division of Cellular and Molecular Biology, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
² Department of Cell Signaling, Tokyo Medical Dental University, Bunkyo-ku, Tokyo 113-8519, Japan

TRAF6 is essential for osteoclastogenesis and for both RANK- and CD40-mediated activation of IKK and MAPKs. RANK, but not CD40, can promote osteoclastogenesis because only RANK induces NFATc1 activation through PLC2-induced Ca²⁺ oscillations together with the co-stimulatory signals emanating from immune receptors linked to ITAM-containing adaptors. These previous data suggest that RANK harbors a unique domain that functions in concert with the TRAF6-binding site in osteoclastogenesis. Here we identify such a domain, highly conserved domain in RANK (HCR), which is dispensable for the early phase of RANK and ITAM signaling but is essential for their late-phase signaling, including sustained activation of NF-B and PLC2 leading to NFATc1 activation. HCR recruits an adaptor protein, Gab2, which further associates with PLC2 in the late phase. Formation of the HCR-mediated signaling complex could account for the sustained activation of NF-B and PLC2. The present study identifies HCR as a unique domain that plays a critical role in the long-term linkage between RANK and ITAM signals, providing a molecular basis for therapeutic strategies.

^* jun-i{at}ims.u-tokyo.ac.jp