Large Scale Phosphoproteome Profiles Comprehensive Features of Mouse Embryonic Stem Cells
Large Scale Phosphoproteome Profiles Comprehensive Features of Mouse Embryonic Stem Cells
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DOI：
10.1074/mcp.m110.001750
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发表时间：
2011-04-01
影响因子：
7
通讯作者：
Zeng, Rong
中科院分区：
文献类型：
--
作者：
Li, Qing-Run;Xing, Xiao-Bin;Zeng, Rong
胚胎干细胞是多能的，能够无限自我更新。阐明潜在的分子机制可能有助于以细胞为基础的再生医学的进步。在目前的工作中，我们进行了大规模的分析磷酸化蛋白质组在小鼠胚胎干细胞（mES）。使用多重策略，我们检测到4581蛋白和3970高置信度不同的磷酸化位点在1642磷蛋白。值得注意的是，22个突出的磷酸化干细胞标志物蛋白与39个新的磷酸化位点首次通过质谱鉴定，包括NANOG（Ser-65）和RE 1沉默转录因子（Ser-950和Thr-953）中的磷酸化位点。在mES细胞分化过程中获得的NANOG肽的定量分布显示，磷酸肽和非磷酸肽的丰度以不同的趋势下降。据我们所知，这项研究提出了mES细胞中磷酸化的最大全球表征。与最终分化的组织细胞的研究相比，磷酸化数据集的生物信息学分析揭示了人和小鼠ES细胞中一致的磷酸化基序。此外，对磷酸化保守性的研究表明，磷蛋白在未分化的ES细胞状态中比在最终分化的组织细胞状态中更保守。然而，从与磷酸盐的保守性比较中得出相反的结论。总体而言，这项工作提供了一个概述磷酸化在胚胎干细胞，是一个宝贵的资源，为未来的理解基础生物学在胚胎干细胞。Molecular & Cellular Proteomics 10：10.1074/mcp. M110.001750，1-14，2011.
Embryonic stem cells are pluripotent and capable of unlimited self-renewal. Elucidation of the underlying molecular mechanism may contribute to the advancement of cell-based regenerative medicine. In the present work, we performed a large scale analysis of the phosphoproteome in mouse embryonic stem (mES) cells. Using multiplex strategies, we detected 4581 proteins and 3970 high confidence distinct phosphosites in 1642 phosphoproteins. Notably, 22 prominent phosphorylated stem cell marker proteins with 39 novel phosphosites were identified for the first time by mass spectrometry, including phosphorylation sites in NANOG (Ser-65) and RE1 silencing transcription factor (Ser-950 and Thr-953). Quantitative profiles of NANOG peptides obtained during the differentiation of mES cells revealed that the abundance of phosphopeptides and non-phosphopeptides decreased with different trends. To our knowledge, this study presents the largest global characterization of phosphorylation in mES cells. Compared with a study of ultimately differentiated tissue cells, a bioinformatics analysis of the phosphorylation data set revealed a consistent phosphorylation motif in human and mouse ES cells. Moreover, investigations into phosphorylation conservation suggested that phosphoproteins were more conserved in the undifferentiated ES cell state than in the ultimately differentiated tissue cell state. However, the opposite conclusion was drawn from this conservation comparison with phosphosites. Overall, this work provides an overview of phosphorylation in mES cells and is a valuable resource for the future understanding of basic biology in mES cells. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.001750, 1-14, 2011.