| First Author | Srivastava S | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 15 | Pages | 3132-9 |
| PubMed ID | 22645315 | Mgi Jnum | J:186642 |
| Mgi Id | MGI:5432834 | Doi | 10.1128/MCB.00019-12 |
| Citation | Srivastava S, et al. (2012) Phosphatidylinositol-3-Kinase C2beta and TRIM27 Function To Positively and Negatively Regulate IgE Receptor Activation of Mast Cells. Mol Cell Biol 32(15):3132-9 |
| abstractText | Cross-linking of the IgE receptor (FcepsilonRI) 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 C2beta (PI3KC2beta) is necessary for FcepsilonRI-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 FcepsilonRI activation of KCa3.1 and downstream signaling by ubiquitinating and inhibiting PI3KC2beta. 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 PI3KC2beta is a potential new pharmacologic target to treat IgE-mediated disease. |
