| First Author | Yip KH | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13198 | PubMed ID | 27786273 |
| Mgi Jnum | J:242637 | Mgi Id | MGI:5905933 |
| Doi | 10.1038/ncomms13198 | Citation | Yip KH, et al. (2016) The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell activation. Nat Commun 7:13198 |
| abstractText | Cross-linkage of the high-affinity immunoglobulin E (IgE) receptor (FcvarepsilonRI) on mast cells by antigen ligation has a critical role in the pathology of IgE-dependent allergic disorders, such as anaphylaxis and asthma. Restraint of intracellular signal transduction pathways that promote release of mast cell-derived pro-inflammatory mediators is necessary to dampen activation and restore homoeostasis. Here we show that the ligase Nedd4-2 and the adaptor Ndfip1 (Nedd4 family interacting protein 1) limit the intensity and duration of IgE-FcvarepsilonRI-induced positive signal transduction by ubiquitinating phosphorylated Syk, a tyrosine kinase that is indispensable for downstream FcvarepsilonRI signalosome activity. Importantly, loss of Nedd4-2 or Ndfip1 in mast cells results in exacerbated and prolonged IgE-mediated cutaneous anaphylaxis in vivo. Our findings reveal an important negative regulatory function for Nedd4-2 and Ndfip1 in IgE-dependent mast cell activity. |
