| First Author | Srivastava S | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 8 | Pages | e0183474 |
| PubMed ID | 28820911 | Mgi Jnum | J:248033 |
| Mgi Id | MGI:5918970 | Doi | 10.1371/journal.pone.0183474 |
| Citation | Srivastava S, et al. (2017) Phosphatidlyinositol-3-kinase C2 beta (PI3KC2beta) is a potential new target to treat IgE mediated disease. PLoS One 12(8):e0183474 |
| 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 delayed type hypersensitivity reactions. The Ca2+ activated K+ channel, KCa3.1, plays a critical role in IgE-stimulated Ca2+ entry and degranulation in mast cells by helping to maintain a negative membrane potential, which provides an electrochemical gradient to drive Ca2+ influx. Of the 3 classes of PI3K, the class II PI3Ks are the least studied and little is known about the roles for class II PI3Ks in vivo in the context of the whole organism under normal and pathological conditions. Studying bone marrow derived mast cells (BMMC) isolated from PI3KC2beta-/- mice, we now show that the class II PI3KC2beta is critical for FcepsilonRI stimulated KCa3.1 channel activation and the subsequent activation of mast cells. We found FcepsilonRI-stimulated Ca2+ entry, cytokine production, and degranulation are decreased in BMMC isolated from PI3KC2beta-/- mice. In addition, PI3KC2beta-/- mice are markedly resistant to both passive cutaneous and passive systemic anaphylaxis. These findings identify PI3KC2beta as a new pharmacologic target to treat IgE-mediated disease. |
