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首页> 外文期刊>Proteomics >Phosphoproteomics identified Endofin, DCBLD2, and KIAA0582 as novel tyrosine phosphorylation targets of EGF signaling and Iressa in human cancer cells
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Phosphoproteomics identified Endofin, DCBLD2, and KIAA0582 as novel tyrosine phosphorylation targets of EGF signaling and Iressa in human cancer cells

机译:磷酸蛋白质组学鉴定Endofin,DCBLD2和KIAA0582是人类癌细胞中EGF信号转导和易瑞沙的新型酪氨酸磷酸化靶标

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摘要

With the completion of the human genome project, analysis of enriched phosphotyrosyl proteins from epidermal growth factor (EGF)-induced phosphotyrosine proteome permits the identification of novel downstream substrates of the EGF receptor (EGFR). Using cICAT-based LC-MS/MS method, we identified and relatively quantified the tyrosine phosphorylation levels of 21 proteins between control and EGF-treated A431 human cervical cancer cells. Of these, Endofin, DCBLD2, and KIAA0582 were validated to be novel tyrosine-phosphorylation targets of EGF signaling and Iressa, a highly selective inhibitor of EGFR. In addition, EGFR activity was shown to be necessary for EGF-induced localization of Endofin, an FYVE domain-containing protein regulated by phosphoinositol lipid and engaged in endosome-mediated receptor modulation. Although several groups have conducted phosphoproteomics of EGF signaling in recent years, our study is the first to identify and validate Endofin, DCBLD2, and KIAA0582 as part of a complex EGF phosphotyrosine signaling network. These novel data will provide new insights into the complex EGF signaling and may have implications on target-directed cancer therapeutics.
机译:随着人类基因组计划的完成,对表皮生长因子(EGF)诱导的磷酸酪氨酸蛋白质组中富集的磷酸酪氨酸蛋白的分析可以鉴定EGF受体(EGFR)的新型下游底物。使用基于cICAT的LC-MS / MS方法,我们确定并相对定量了对照和EGF处理的A431人宫颈癌细胞之间21种蛋白质的酪氨酸磷酸化水平。其中,Endofin,DCBLD2和KIAA0582被证实是EGF信号传导和EGFR的高度选择性抑制剂Iressa的新型酪氨酸磷酸化靶标。此外,EGFR活性被证明对于EGF诱导的Endofin定位是必需的,Endofin是一种由磷酸肌醇脂质调节并参与内体介导的受体调节的含FYVE域的蛋白质。尽管近年来有几个小组进行了EGF信号转导的磷酸化蛋白质组学研究,但我们的研究是第一个鉴定和验证Endofin,DCBLD2和KIAA0582作为复杂EGF磷酸酪氨酸信号转导网络的一部分的研究。这些新颖的数据将为复杂的EGF信号传导提供新的见识,并可能对靶向靶点的癌症治疗产生影响。

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