Novel monoclonal antibodies recognizing the active conformation of epidermal growth factor receptor

Novel monoclonal antibodies recognizing the active conformation of epidermal growth factor receptor
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DOI:
10.1016/j.bbrc.2010.03.052
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发表时间:
2010-04-09
影响因子:
3.1
通讯作者:
Goishi, Katsutoshi
Goishi, Katsutoshi
中科院分区:
生物学4区
文献类型:
--
作者:
Ise, Nobuyuki;Omi, Kazuya;Goishi, Katsutoshi

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表皮生长因子受体(epidermal growth factor receptor,EGFR)的精确调控是其在细胞生长调控中发挥作用的关键。尽管已经开发了许多针对EGFR的抗体并用于分析其调控和功能,但特异性分析活化的EGFR并不容易。我们已经建立了新的单克隆抗体,其识别活化的EGFR而不依赖于其磷酸化。我们的抗体通过识别通过配体结合诱导的构象变化而暴露的表位,在免疫沉淀和免疫荧光中检测EGFR的活性状态。此外,我们发现,我们的抗体优先检测肺癌细胞系中发现的组成型活性EGFR突变体的构象。这些结果表明,我们的抗体可能成为新的研究和诊断工具,检测和分析各种细胞和组织中活性EGFR的构象。(C)2010爱思唯尔公司版权所有
The precise regulation of epidermal growth factor receptor (EGFR) is crucial for its function in cellular growth control Although many antibodies against EGFR have been developed and used to analyze its regulation and function, it is not yet easy to analyze activated EGFR specifically Activated EGFR has been mainly detected by its phosphorylation state using anti-phospho-EGFR and anti-phosphotyrosine antibodies In the present study, we have established novel monoclonal antibodies which recognize the activated EGFR independently of its phosphorylation Our antibodies detected active state of EGFR in immunoprecipitation and immunofluorescence, by recognizing the epitopes which are exposed through the conformational change induced by ligand-binding Furthermore, we found that our antibodies preferentially detected the conformation of constitutively active EGFR mutants found in lung cancer cell lines These results indicate that our antibodies may become novel research and diagnostic tools for detecting and analyzing the conformation of active EGFR in various cells and tissues. (C) 2010 Elsevier Inc All rights reserved