| First Author | Taguchi Y | Year | 2009 |
| Journal | Genes Cells | Volume | 14 |
| Issue | 11 | Pages | 1331-45 |
| PubMed ID | 19845770 | Mgi Jnum | J:158321 |
| Mgi Id | MGI:4438543 | Doi | 10.1111/j.1365-2443.2009.01351.x |
| Citation | Taguchi Y, et al. (2009) A unique domain in RANK is required for Gab2 and PLCgamma2 binding to establish osteoclastogenic signals. Genes Cells 14(11):1331-45 |
| abstractText | 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 PLCgamma2-induced Ca(2+) 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-kappaB and PLCgamma2 leading to NFATc1 activation. HCR recruits an adaptor protein, Gab2, which further associates with PLCgamma2 in the late phase. Formation of the HCR-mediated signaling complex could account for the sustained activation of NF-kappaB and PLCgamma2. 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. |
