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Type: Journal article
Title: The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell activation
Author: Yip, K.
Kolesnikoff, N.
Hauschild, N.
Biggs, L.
Lopez, A.
Galli, S.
Kumar, S.
Grimbaldeston, M.
Citation: Nature Communications, 2016; 7:13198-1-13198-14
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 2041-1723
Statement of
Kwok Ho Yip, Natasha Kolesnikoff, Nicholas Hauschild, Lisa Biggs, Angel F. Lopez, Stephen J. Galli, Sharad Kumar, Michele A. Grimbaldeston
Abstract: Cross-linkage of the high-affinity immunoglobulin E (IgE) receptor (FceRI) 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-FceRI-induced positive signal transduction by ubiquitinating phosphorylated Syk, a tyrosine kinase that is indispensable for downstream FceRI 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.
Keywords: Cells, Cultured; Mast Cells; Animals; Mice, Inbred C57BL; Mice, Transgenic; Mice, Knockout; Immunoglobulin E; Carrier Proteins; Membrane Proteins; Receptors, IgE; Cytokines; Passive Cutaneous Anaphylaxis; Adoptive Transfer; Female; Male; Syk Kinase; Nedd4 Ubiquitin Protein Ligases
Rights: © The Author(s) 2016, This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
RMID: 0030057805
DOI: 10.1038/ncomms13198
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Appears in Collections:Medicine publications

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