description
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)
external resources
NCBI:1269300
REACTOME:R-HSA-2871809
PUBMED:17336609
PUBMED:10807788
PUBMED:1309940
genes
BTK
,
CALM1
,
CALM2
,
CALM3
,
GRB2
,
IGHE
,
IGLC1
,
IGLC6
,
ITK
,
ITPR1
,
ITPR2
,
ITPR3
,
LCP2
,
LYN
,
NFATC1
,
NFATC2
,
NFATC3
,
PLCG1
,
PLCG2
,
PPP3CA
,
PPP3CB
,
PPP3R1
,
SHC1
,
SOS1
,
SYK
,
TEC
,
TXK
,
VAV1
,
VAV2
,
GRAP2
,
VAV3
,
AHCYL1
,
LAT
,
IGKV3D-11
,
IGKV5-2
,
IGKV4-1
,
