Analysis of Constitutive EGFR Signaling Regulating IRF3 Transcriptional Activity in Cancer Cells.
Analysis of Constitutive EGFR Signaling Regulating IRF3 Transcriptional Activity in Cancer Cells.
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癌细胞中调节 IRF3 转录活性的组成型 EGFR 信号转导分析。
DOI：
10.1007/978-1-4939-7219-7_14
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Habib,AmynA
中科院分区：
文献类型：
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作者：
Guo,Gao;Gong,Ke;Habib,AmynA
表皮生长因子受体（EGFR）在多种人类肿瘤中起重要作用。EGFR的过表达导致EGFR中多个酪氨酸残基的组成性酪氨酸磷酸化。最近，我们已经证明，过度表达的EGFR取决于配体的存在或不存在，在两种不同的和相互排斥的信号传导模式之间振荡。EGFR组成型激活转录因子IRF3，导致其靶基因的转录。EGF的加入导致IRF3转录活性的丧失和经典信号通路如ERK的激活。这种双峰信号传导的机制基础似乎是在配体存在或不存在的情况下，一组不同的信号传导蛋白与EGFR的结合。在这一章中，我们描述了一个详细的协议，分析组成型EGFR信号与IRF3靶基因的重点。
Epidermal growth factor receptor (EGFR) plays an important role in various types of human cancers. Overexpression of EGFR leads to a constitutive tyrosine phosphorylation of multiple tyrosine residues in the EGFR. Recently, we have demonstrated that overexpressed EGFR oscillates between two distinct and mutually exclusive modes of signaling depending on the presence or absence of ligand. EGFR constitutively activates transcription factor IRF3, which results in transcription of its target genes. Addition of EGF causes a loss of IRF3 transcriptional activity and activation of canonical signaling pathways such as ERK. The mechanistic basis of this bimodal signaling appears to be the association of a distinct set of signaling proteins with EGFR in the absence or presence of ligand. In this chapter, we describe a detailed protocol for analyses of constitutive EGFR signaling with a focus on IRF3 target genes.