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Copyright ©2012 Baishideng Publishing Group Co.
World J Orthop. Nov 18, 2012; 3(11): 167-174
Published online Nov 18, 2012. doi: 10.5312/wjo.v3.i11.167
Figure 3
Figure 3 Amplifying phase. Both Ca2+ oscillation-dependent and -independent nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) amplification are induced. Highly conserved domain in receptor activator of nuclear factor-κB (RANK)-mediated RANK signaling and immunoreceptor tyrosine-based activation motif (ITAM) signaling lead to continuous phospholipase C (PLC)γ2 activation. Regulator of G-protein signaling 10 (RGS10) determines the Ca2+ oscillation pattern through control of PLCγ2 by competitive binding of Ca2+/calmodulin and phosphatidylinositol 3, 4, 5-trisphosphate (PIP3). Sustained Ca2+ oscillation contributes to NFATc1 amplification mediated by transcriptional auto-induction. In the Ca2+ oscillation-independent pathway, Cot kinase enhances NFATc1 stabilization through direct phosphorylation and contributes to its accumulation. ER: Endoplasmic reticulum; BLNK: B cell linker protein; SLP76: Src homology 2 domain-containing leukocyte protein of 76 kD; TRAF6: Tumor necrosis factor receptor-associated factor 6; Gab2: Grb-2-associated binder-2; IP3R: IP3 receptor; CaM: Calmodulin; Btk: Bruton's tyrosine kinase.