Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, CA, USA.
Cell Cycle. 2010 Sep 1;9(17):3479-84. doi: 10.4161/cc.9.17.13152. Epub 2010 Sep 26.
Cells are highly responsive to their environment. One of the main strategies used by cells in signal transduction is protein phosphorylation, a reversible modification that regulates numerous biological processes. Misregulation of phosphorylation-mediated processes is often implicated in many human diseases and cancers. A global and quantitative analysis of protein phosphorylation provides a powerful new approach and has the potential to reveal new insights in signaling pathways. Recent technological advances in high resolution mass spectrometers and multidimensional liquid chromatography, combined with the use of stable isotope labeling of proteins, have led to the application of quantitative phosphoproteomics to study in vivo signal transduction events on a proteome-wide scale. Here we review recent advancements in quantitative phosphoproteomic technologies, discuss their potentials and identify areas for future development. A key objective of proteomic technology is its application to addressing biological questions. We will therefore describe how current quantitative phosphoproteomic technology can be used to study the molecular basis of phosphorylation events in the DNA damage response.
细胞对其环境高度敏感。细胞在信号转导中使用的主要策略之一是蛋白质磷酸化,这是一种可逆的修饰,可调节许多生物过程。磷酸化介导过程的失调通常与许多人类疾病和癌症有关。对蛋白质磷酸化的全面和定量分析提供了一种强大的新方法,有可能揭示信号通路中的新见解。近年来,高分辨率质谱仪和多维液相色谱技术的进步,结合蛋白质稳定同位素标记的应用,使得定量磷酸蛋白质组学能够在全蛋白质组范围内研究体内信号转导事件。在这里,我们回顾了定量磷酸蛋白质组学技术的最新进展,讨论了它们的潜力,并确定了未来的发展方向。蛋白质组学技术的一个关键目标是将其应用于解决生物学问题。因此,我们将描述如何使用当前的定量磷酸蛋白质组学技术来研究 DNA 损伤反应中磷酸化事件的分子基础。