FCERI mediated Ca+2 mobilization

Increase of intracellular calcium in mast cells is most crucial for mast cell degranulation. Elevation of intracellular calcium is achieved by activation of PLC-gamma. Mast cells express both PLC-gamma1 and PLC-gamma2 isoforms and activation of these enzymes leads to conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG). The production of IP3 leads to mobilization of intracellular Ca+2, which later results in a sustained Ca+2 flux response that is maintained by an influx of extracellular Ca+2. In addition to degranulation, an increase in intracellular calcium concentration also activates the Ca2+/calmodulin-dependent serine phosphatase calcineurin. Calcineurin dephosphorylates the nuclear factor for T cell activation (NFAT) which exposes nuclear-localization signal sequence triggering translocation of the dephosphorylated NFAT-CaN complex to the nucleus. Once in the nucleus, NFAT regulates the transcription of several cytokine genes (Kambayashi et al. 2007, Hoth & Penner 1992, Ebinu et al. 2000, Siraganian et al).

肥大细胞内钙离子的增加对于肥大细胞的脱颗粒作用至关重要。通过PLC-γ的激活，实现细胞内钙离子的升高。肥大细胞表达PLC-γ1和PLC-γ2两种同种异构体，这些酶的激活导致磷脂酰肌醇4,5-二磷酸（PIP2）转化为肌醇三磷酸（IP3）和二酰甘油（DAG）。IP3的产生引起细胞内Ca+2的动员，进而引发持续的Ca+2流量反应，该反应通过细胞外Ca+2的流入得以维持。除了脱颗粒作用之外，细胞内钙浓度增加还会激活Ca2+/钙调蛋白依赖的丝氨酸磷酸酶——钙调神经磷酸酶。钙调神经磷酸酶去磷酸化T细胞激活的核因子（NFAT），从而暴露核定位信号序列，触发去磷酸化的NFAT-CaN复合物向细胞核的转位。一旦进入细胞核，NFAT调控多种细胞因子基因的转录（Kambayashi等，2007年，Hoth与Penner，1992年，Ebinu等，2000年，Siraganian等）。