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Regulation of the Calcium Signal by Phospholipase (PL) D, Sphingosine Kinase (SK), and Phosphatidylinositol 4‐Phosphate (PIP) 5‐Kinase in Mast Cells
Author(s) -
Peng Ze,
Beaven Michael A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a117-c
Subject(s) - phosphatidylinositol , degranulation , phosphatidic acid , phospholipase d , microbiology and biotechnology , thapsigargin , signal transduction , kinase , phospholipase c , chemistry , gq alpha subunit , ionomycin , sphingosine , biochemistry , biology , intracellular , phospholipid , g protein , receptor , membrane
Activation of PLD and elevation of cytosolic Ca 2+ are essential signals for degranulation in antigen‐stimulated mast cells but the processes linking these events are unclear. Two potential downstream targets for the PLD product, phosphatidic acid, include SK and PIP 5‐kinase both of which may regulate mobilization of Ca 2+ . To determine whether this is so, pharmacologic inhibitors as well as siRNAs directed against PLD1, PLD2, and PIP 5‐kinase were tested for their effects on mobilization of Ca 2+ . All reagents suppressed Ca 2+ mobilization and degranulation in antigen‐stimulated cells. PLD appeared to be critical for sustaining elevated levels of cytosolic Ca 2+ and for regulating production sphingosine 1 phosphate by SK but not of inositol 1,4,5‐trisphosphate (IP 3 ) by PLC γ 1/2. These studies suggested that in addition to release of intracellular Ca 2+ by IP 3 , the PLD→SK pathway serves to sustain the calcium signal and thus degranulation. Interestingly, the studies with anti‐PIP 5‐kinase siRNA indicated that this enzyme regulated influx of Ca 2+ not only in antigen‐stimulated cells but also in cells stimulated with thapsigargin which is a potent stimulant of PLD but not of PLC. Therefore, PIP 5‐kinase may regulate the calcium signal through provision of phosphatidylinositol 1,4‐bisphosphate as a substrate for PLC and also as a necessary factor for facilitating Ca 2+ influx.