Seminar "Regulation of the TRAF6-NF-kB-NFATc1 signal pathway in osteoclastogenesis."

Dear all,

Open Technology Center and Cell Signal Unit would like to invite you to a seminar by Prof. Jun-ichiro Inoue.

We look forward to seeing many of you there.

Speaker: Prof. Jun-ichiro Inoue

Division of Cellular and Molecular Biology, Department of Cancer Biology

Institute of Medical Science, University of Tokyo

Title: Regulation of the TRAF6-NF-kB-NFATc1 signal pathway in osteoclastogenesis

Abstract: TNFR-associatedy RANK induces NFATc1 activation through PLCg2-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. We have identified 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-kB and PLCg2 leading to NFATc1 activation. HCR recruits an adaptor protein, Gab2, which further associates with PLCg2 in the late phase. Formation of the HCR-mediated signaling complex could account for the sustained activation of NF-kB and PLCg2. 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 for skeletal diseases and cancer bone metastasis.