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Phosphatidylinositol-3-Kinase C2β and TRIM27 Function To Positively and Negatively Regulate IgE Receptor Activation of Mast Cells
- Source :
- Molecular and Cellular Biology. 32:3132-3139
- Publication Year :
- 2012
- Publisher :
- Informa UK Limited, 2012.
-
Abstract
- Cross-linking of the IgE receptor (FcεRI) on mast cells plays a critical role in IgE-dependent allergy, including allergic rhinitis, asthma, anaphylaxis, and immediate-type hypersensitivity reactions. Previous studies have demonstrated that the K(+) channel, KCa3.1, plays a critical role in IgE-stimulated Ca(2+) entry and degranulation in both human and mouse mast cells. We now have shown that the class II phosphatidylinositol-3-kinase C2β (PI3KC2β) is necessary for FcεRI-stimulated activation of KCa3.1, Ca(2+) influx, cytokine production, and degranulation of bone marrow-derived mast cells (BMMC). In addition, we found that the E3 ubiquitin ligase, tripartite motif containing protein 27 (TRIM27), negatively regulates FcεRI activation of KCa3.1 and downstream signaling by ubiquitinating and inhibiting PI3KC2β. TRIM27(-/-) mice are also more susceptible in vivo to acute anaphylaxis. These findings identify TRIM27 as an important negative regulator of mast cells in vivo and suggest that PI3KC2β is a potential new pharmacologic target to treat IgE-mediated disease.
- Subjects :
- Allergy
Patch-Clamp Techniques
Class I Phosphatidylinositol 3-Kinases
Cell Degranulation
Ubiquitin-Protein Ligases
medicine.medical_treatment
Biophysics
Immunoglobulin E
chemistry.chemical_compound
Mice
Phosphatidylinositol 3-Kinases
Hypersensitivity
medicine
Animals
Phosphatidylinositol
Mast Cells
RNA, Small Interfering
Receptor
Anaphylaxis
Molecular Biology
biology
Chemistry
Receptors, IgE
Kinase
Ubiquitination
Degranulation
Nuclear Proteins
Articles
Cell Biology
Intermediate-Conductance Calcium-Activated Potassium Channels
medicine.disease
Ubiquitin ligase
Cell biology
DNA-Binding Proteins
Mice, Inbred C57BL
Cytokine
Immunology
biology.protein
RNA Interference
Signal transduction
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....b264a33f5c5c153a2b73c3dab4b04773