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Figure 2. RANK Signal Transduction Via TRAFs.

Figure 2

RANK Signal Transduction Via TRAFs. Shown is a schematic diagram depicting the role of TRAF6 in regulating RANK-signaling events. RANKL stimulates the Lys63-linked polyubiquitination of TRAF6 in the presence of the dimeric E2 enzyme consisting of Ubc13 and Uev1A. The Lys63-liked polyubiquitin chain on TRAF6 recruits the Zn-finger domain of TAB2 to the complex, which results in the auto-activation of TAK1 by an unknown mechanism. Subsequently, TAK1 activates downstream kinases to activate the transcription factors NF-κB and AP1. By an unknown mechanism, TRAF6 also mobilizes intracellular calcium to activate calcineurin causing the de-phosphorylation of NFATc1 and its translocation into the nucleus, where it cooperates with NF-κB and AP1 to drive the transcription program for osteoclast differentiation. RANKL also stimulates the activity of the Src kinase pathway through TRAF6 to initiate cytoskeleton rearrangements and actin ring formation for the bone resorbing activity of the osteoclast. The role of the other TRAFs in RANKL signaling is not well characterized.

From: TRAFs in RANK Signaling

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