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The beta- and gamma-isoforms of type I PIP5K regulate distinct stages of Ca2+ signaling in mast cells.
- Source :
-
Journal of cell science [J Cell Sci] 2009 Jul 15; Vol. 122 (Pt 14), pp. 2567-74. Date of Electronic Publication: 2009 Jun 23. - Publication Year :
- 2009
-
Abstract
- Crosslinking of IgE receptors by antigen initiates Ca2+ mobilization in mast cells by activating phospholipase-C gamma-mediated hydrolysis of phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2]. The resulting inositol 1,4,5-trisphosphate-mediated Ca2+ release from the endoplasmic reticulum (ER) activates store-operated Ca2+ entry, which is necessary for exocytotic release of inflammatory mediators. To investigate roles for PtdIns(4,5)P2-synthesizing isozymes of the type I phosphatidylinositol 4-phosphate 5-kinase family (PIP5K-I) in mast cell signaling, we compared the ectopic expression of wild-type and catalytically inactive PIP5K-I beta in RBL-2H3 mast cells. Surprisingly, both antigen and thapsigargin-stimulated Ca2+ influx were reduced by overexpression of active PIP5K-I beta, whereas antigen-stimulated Ca2+ release from ER stores was unaffected. Consistent with these results, Ca2+ entry stimulated by antigen or thapsigargin was enhanced by expression of a plasma-membrane-associated inositol polyphosphate 5'-phosphatase, whereas antigen-stimulated Ca2+ release from stores was reduced. To investigate the role of PIP5K-I gamma in antigen-stimulated Ca2+ mobilization, we used bone-marrow-derived mast cells from PIP5K-I gamma(-/-) mice. Antigen-stimulated Ca2+ release from ER stores was substantially reduced in the absence of PIP5K-I gamma, but thapsigargin-mediated Ca2+ entry was unaffected. In summary, PIP5K-I gamma positively regulates antigen-stimulated Ca2+ release from ER stores, whereas PIP5K-I beta negatively regulates store-operated Ca2+ entry, suggesting that these different PIP5K-I isoforms synthesize functionally distinct pools of PtdIns(4,5)P2 at the plasma membrane.
- Subjects :
- Animals
Antigens metabolism
Bone Marrow Cells enzymology
Cell Line, Tumor
Cell Membrane enzymology
Endoplasmic Reticulum enzymology
Enzyme Inhibitors pharmacology
Inositol Polyphosphate 5-Phosphatases
Isoenzymes
Mast Cells drug effects
Mice
Mice, Knockout
Phosphatidylinositol 4,5-Diphosphate metabolism
Phospholipase C gamma metabolism
Phosphoric Monoester Hydrolases metabolism
Phosphotransferases (Alcohol Group Acceptor) deficiency
Phosphotransferases (Alcohol Group Acceptor) genetics
Rats
Receptors, IgE metabolism
Recombinant Fusion Proteins metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases antagonists & inhibitors
Sarcoplasmic Reticulum Calcium-Transporting ATPases metabolism
Thapsigargin pharmacology
Time Factors
Transfection
Calcium Signaling drug effects
Mast Cells enzymology
Phosphotransferases (Alcohol Group Acceptor) metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9533
- Volume :
- 122
- Issue :
- Pt 14
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 19549683
- Full Text :
- https://doi.org/10.1242/jcs.048124