The TRAF6-NF-κB-NFATc1 signal pathway in RANK-induced osteoclastogenesis

Dear All,

Cell Signal Unit (Yamamoto Unit) would like to inform you of a seminar by Dr. Jun-ichiro Inoue from the Institute of Medical Science, the University of Tokyo.

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Date: Wednesday, February 14, 2018

Time: 14:00-15:00

Venue: D015, Level D, Lab 1

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Speaker:

Dr. Jun-ichiro Inoue, The Institute of Medical Science, The University of Tokyo

Title:
The TRAF6-NF-kB-NFATc1 signal pathway in RANK-induced osteoclastogenesis
 

Abstract:
TNFR-associated factor 6 (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 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.

Host:
Prof. Tadashi Yamamoto

We hope to see many of you at the seminar.

Best regards,

Yuki Nakagawa

Research Unit Administrator

Cell Signal Unit