A peptide biosensor for detecting intracellular Abl kinase activity using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
A peptide biosensor for detecting intracellular Abl kinase activity using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
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DOI：
10.1016/j.ab.2009.09.048
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发表时间：
2010-02-01
影响因子：
2.9
通讯作者：
Parker, Laurie L.
中科院分区：
文献类型：
--
作者：
Placzek, Ekaterina A.;Plebanek, Michael P.;Parker, Laurie L.
许多癌症的特征在于激酶失调导致的蛋白质磷酸化的变化。在慢性髓性白血病（CML）中，通过费城染色体的AN激酶信号传导的破坏（导致Bcr-Abl突变）为开发激酶抑制剂药物（例如特异性抑制剂伊马替尼（也称为STI 571或格列卫））提供了范例。然而，由于患者无限期地接受这种药物治疗以维持缓解，耐药性越来越成为一个问题。虽然有许多方法检测激酶活性，但大多数缺乏“多重”分析的能力（即，以同时检测多于一个衬底）。在这里，我们报告了一种新的生物传感器检测Abl激酶活性和抑制剂在活的完整细胞过表达的CML模型Abl激酶结构的敏感性。这种简单的方法最终可以提供一种新的工具，用于检测过度表达致癌激酶的癌细胞中的激酶活性和抑制剂药物反应。(C)2009 Elsevier Inc. All rights reserved.
Many cancers are characterized by changes in protein phosphorylation as a result of kinase dysregulation. Disruption of AN kinase signaling through the Philadelphia chromosome (causing the Bcr-Abl mutation) in chronic myeloid leukemia (CML) has provided a paradigm for development of kinase inhibitor drugs such as the specific inhibitor imatinib (also known as STI571 or Gleevec). However, because patients are treated indefinitely with this drug to maintain remission, resistance is increasingly becoming an issue. Although there are many ways to detect kinase activity, most lack the ability to "multiplex" the analysis (i.e., to detect more than one substrate simultaneously). Here we report a novel biosensor for detecting Abl kinase activity and sensitivity to inhibitor in live intact cells overexpressing a CML model Abl kinase construct. This straightforward methodology could eventually provide a new tool for detecting kinase activity and inhibitor drug response in cancer cells that overexpress oncogenic kinases. (C) 2009 Elsevier Inc. All rights reserved.