Eosinophil peroxidase activates cells by HER2 receptor engagement and β1-integrin clustering with downstream MAPK cell signaling

Title: Eosinophil peroxidase activates cells by HER2 receptor engagement and β1-integrin clustering with downstream MAPK cell signaling
Authors: Hennigan, Kerrie
Conroy, Paul J.
Walsh, Marie-Therese
Mooney, Catherine
Permanent link: http://hdl.handle.net/10197/10064
Date: Oct-2016
Online since: 2019-04-23T08:49:37Z
Abstract: Eosinophils account for 1–3% of peripheral blood leukocytes and accumulate at sites of allergic inflammation, where they play a pathogenic role. Studies have shown that treatment with mepolizumab (an anti-IL-5 monoclonal antibody) is beneficial to patients with severe eosinophilic asthma, however, the mechanism of precisely how eosinophils mediate these pathogenic effects is uncertain. Eosinophils contain several cationic granule proteins, including Eosinophil Peroxidase (EPO). The main significance of this work is the discovery of EPO as a novel ligand for the HER2 receptor. Following HER2 activation, EPO induces activation of FAK and subsequent activation of β1-integrin, via inside-out signaling. This complex results in downstream activation of ERK1/2 and a sustained up regulation of both MUC4 and the HER2 receptor. These data identify a receptor for one of the eosinophil granule proteins and demonstrate a potential explanation of the proliferative effects of eosinophils.
Funding Details: Health Research Board
Type of material: Journal Article
Publisher: Elsevier
Journal: Clinical Immunology
Volume: 171
Start page: 1
End page: 11
Copyright (published version): 2016 the Authors
Keywords: Cell lineHumansEosinophil perioxidaseExtracellular Signal-Regulated MAP KinasesReceptorerbB-2AntigensCD29Recombinant proteinsRNASmall interferingSignal transductionFocal adhesion kinase 1Mucin-4
DOI: 10.1016/j.clim.2016.08.009
Language: en
Status of Item: Peer reviewed
Appears in Collections:Computer Science Research Collection

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