Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry
Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry
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DOI：
10.1016/s1097-2765(00)00132-5
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发表时间：
2000-12-01
期刊：
影响因子：
16
通讯作者：
Ahn, NG
中科院分区：
文献类型：
--
作者：
Lewis, TS;Hunt, JB;Ahn, NG
功能蛋白质组学提供了一种强有力的方法，用于监测信号转导途径激活后的全球分子反应，报告改变的蛋白质翻译后修饰和表达。在这里，我们结合联合收割机功能蛋白质组学与选择性激活和抑制MKK 1/2，以确定由MKK/ERK级联调节的细胞靶点。该信号通路的25个靶标被鉴定，其中只有5个先前被表征为MKK/ERK效应子。其余的目标表明，这种信号级联在细胞核转运，核苷酸切除修复，核小体组装，膜运输和细胞骨架调节过程中的新作用。这项研究代表了功能蛋白质组学的应用，确定一个离散的信号转导通路的调节目标，并证明了这种发现为基础的策略，阐明新的MAP激酶通路效应器的效用。
Functional proteomics provides a powerful method for monitoring global molecular responses following activation of signal transduction pathways, reporting altered protein posttranslational modification and expression. Here we combine functional proteomics with selective activation and inhibition of MKK1/2, in order to identify cellular targets regulated by the MKK/ERK cascade. Twenty-five targets of this signaling pathway were identified, of which only five were previously characterized as MKK/ERK effecters. The remaining targets suggest novel roles for this signaling cascade in cellular processes of nuclear transport, nucleotide excision repair, nucleosome assembly, membrane trafficking, and cytoskeletal regulation. This study represents an application of functional proteomics toward identifying regulated targets of a discrete signal transduction pathway and demonstrates the utility of this discovery-based strategy in elucidating novel MAP kinase pathway effecters.