Phosphoproteomic analysis of AML cell lines identifies leukemic oncogenes
Phosphoproteomic analysis of AML cell lines identifies leukemic oncogenes
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DOI：
10.1016/j.leukres.2006.01.001
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发表时间：
2006-09-01
影响因子：
2.7
通讯作者：
Druker, Brian J.
中科院分区：
文献类型：
--
作者：
Walters, Denise K.;Goss, Valerie L.;Druker, Brian J.
STAT5在大约70%的急性髓性白血病（AML）患者的白血病细胞中存在组成性磷酸化。为了确定可能导致STAT5磷酸化的激酶候选物，我们使用液相色谱-串联质谱（LC-MS/MS）质谱法检测AML细胞系中的磷酸化蛋白。我们分别在HT-93和KBM-3细胞中建立了TEL-ARG和BCR-ABL融合蛋白作为STAT5磷酸化的机制。此外，我们在HEL细胞中发现了JAK2假激酶结构域突变，并通过siRNA下调，确定JAK2是负责磷酸化STAT5的激酶。本研究说明了LC-MS/MS质谱和siRNA在鉴定新靶点和突变方面的优势。(c) 2006 Elsevier Ltd.版权所有。
STAT5 is constitutively phosphorylated in leukemic cells in approximately 70% of acute myeloid leukemia (AML) patients. To identify kinase candidates potentially responsible for STAT5 phosphorylation, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometry to detect phosphoproteins in AML cell lines. We established TEL-ARG and BCR-ABL fusion proteins as the mechanism underlying STAT5 phosphorylation in HT-93 and KBM-3 cells, respectively. In addition, we identified a JAK2 pseudokinase domain mutation in HEL cells and using siRNA downregulation, established JAK2 as the kinase responsible for phosphorylating STAT5. This study illustrates the benefit of LC-MS/MS mass spectrometry and siRNA for the identification of novel targets and mutations. (c) 2006 Elsevier Ltd. All rights reserved.