Reactome | FCERI mediated Ca+2 mobilization

FCERI mediated Ca+2 mobilization

Stable Identifier

R-HSA-2871809

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, plasma membrane, nucleoplasm

ReviewStatus

5/5

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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).

Literature References

PubMed ID	Title	Journal	Year
17336609	Proximal signaling events in Fc epsilon RI-mediated mast cell activation Kambayashi, T, Koretzky, GA	J. Allergy Clin. Immunol.	2007
10807788	RasGRP links T-cell receptor signaling to Ras Stone, JC, Bottorff, DA, Hooton, J, Teixeira, C, Ebinu, JO, Barry, M, Stang, SL, Bleakley, RC, Ostergaard, HL, Blumberg, PM	Blood	2000
1309940	Depletion of intracellular calcium stores activates a calcium current in mast cells Penner, R, Hoth, M	Nature	1992