Eosinophil peroxidase activates cells by HER2 receptor engagement and β1-integrin clustering with downstream MAPK cell signaling.
Eosinophil peroxidase activates cells by HER2 receptor engagement and β1-integrin clustering with downstream MAPK cell signaling.
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DOI：
10.1016/j.clim.2016.08.009
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
McBryan J
中科院分区：
文献类型：
--
作者：
Hennigan K;Conroy PJ;Walsh MT;Amin M;O'Kennedy R;Ramasamy P;Gleich GJ;Siddiqui Z;Glynn S;McCabe O;Mooney C;Harvey BJ;Costello RW;McBryan J
嗜酸性粒细胞占外周血白细胞的1-3%，并聚集在过敏性炎症部位，在那里它们发挥致病作用。研究表明，美泊利单抗（一种抗IL-5单克隆抗体）治疗对重度嗜酸性粒细胞性哮喘患者有益，然而，嗜酸性粒细胞如何确切介导这些致病作用的机制尚不确定。嗜酸性粒细胞含有几种阳离子颗粒蛋白，包括嗜酸性粒细胞过氧化物酶（EPO）。这项工作的主要意义是发现EPO作为HER 2受体的新型配体。在HER 2活化后，EPO通过由内向外信号传导诱导FAK活化和随后的β1-整联蛋白活化。该复合物导致ERK 1/2的下游活化以及MUC 4和HER 2受体的持续上调。这些数据确定了嗜酸性粒细胞颗粒蛋白的受体之一，并证明了嗜酸性粒细胞的增殖作用的一个潜在的解释。嗜酸性粒细胞过氧化物酶（EPO）被确认为HER 2受体的配体。EPO对HER 2的激活导致FAK、ERK和β1整联蛋白的激活。EPO诱导MUC 4和HER 2的持续上调。嗜酸性粒细胞的增殖作用的可能机制被揭露。
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. Eosinophil peroxidase (EPO) is confirmed as a ligand for the HER2 receptor. EPO activation of HER2 leads to activation of FAK, ERK and β1 integrin. EPO induces a sustained upregulation of MUC4 and HER2. Possible mechanism for the proliferative effects of eosinophils is uncovered.
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DOI：
10.1158/1078-0432.ccr-09-3331
发表时间：
2010-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Contessa JN;Bhojani MS;Freeze HH;Ross BD;Rehemtulla A;Lawrence TS
通讯作者：
Lawrence TS
DOI：
10.1165/rcmb.2005-0196oc
发表时间：
2006-06-01
影响因子：
6.4
作者：
Durcan, Niamh;Costello, Richard W.;Walsh, Marie-Therese
通讯作者：
Walsh, Marie-Therese
影响因子：
15.9
作者：
Evans, CM;Fryer, AD;Costello, RW
通讯作者：
Costello, RW
影响因子：
8
作者：
Komatsu, M;Jepson, S;Carraway, KL
通讯作者：
Carraway, KL
影响因子：
64.8
作者：
Cho, HS;Mason, K;Leahy, DJ
通讯作者：
Leahy, DJ