Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/104464
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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(1):13198-1-13198-14 |
Publisher: | Nature Publishing Group |
Issue Date: | 2016 |
ISSN: | 2041-1723 2041-1723 |
Statement of Responsibility: | 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 Intercellular Signaling Peptides and Proteins 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 http://creativecommons.org/licenses/by/4.0/ |
DOI: | 10.1038/ncomms13198 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/626907 http://purl.org/au-research/grants/nhmrc/1103006 http://purl.org/au-research/grants/nhmrc/1059393 http://purl.org/au-research/grants/nhmrc/1020755 |
Published version: | http://dx.doi.org/10.1038/ncomms13198 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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hdl_104464.pdf | Published version | 2.98 MB | Adobe PDF | View/Open |
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