Biocenter, Division of Cell Biology, Innsbruck Medical University, Fritz-Pregl Strasse 3, A-6020 Innsbruck, Austria.
Trends Mol Med. 2012 Jan;18(1):43-51. doi: 10.1016/j.molmed.2011.11.001. Epub 2011 Dec 9.
Abnormal protein phosphorylation is implicated in a variety of diseases, but until recently the complexity of tissue material, technical limitations, and the substantial volume of required data processing did not allow large-scale phosphoproteomic analysis of patient material, despite tremendous progress in developing mass spectrometry technologies. Phosphoproteomic approaches were primarily developed using model systems such as transformed cell lines, but technological advances in proteomics now make it feasible to analyze thousands of phosphorylation sites in a quantitative manner in patient materials or complex animal and cellular model systems to identify signaling abnormalities. This review summarizes very recent phosphoproteomic studies on complex tissue material, including tissue samples in biobanks, to complement recent reviews that focus primarily on technical advances in instrumentation and methods. Several successful examples reviewed here suggest it is now possible to apply phosphoproteomic techniques to address more challenging medical questions such as mapping within patient samples signal transduction defects that are relevant for diagnosis and individualized treatment development.
异常蛋白质磷酸化与多种疾病有关，但直到最近，尽管质谱技术取得了巨大进展，但由于组织材料的复杂性、技术限制以及大量数据处理的需要，仍然无法对患者材料进行大规模的磷酸化蛋白质组学分析。磷酸化蛋白质组学方法主要使用转化细胞系等模型系统开发，但蛋白质组学技术的进步现在使得在患者材料或复杂的动物和细胞模型系统中以定量方式分析数千个磷酸化位点以识别信号异常成为可能。这篇综述总结了最近关于复杂组织材料的磷酸化蛋白质组学研究，包括生物库中的组织样本，以补充最近主要关注仪器和方法技术进步的综述。这里回顾的几个成功案例表明，现在可以应用磷酸化蛋白质组学技术来解决更具挑战性的医学问题，例如在患者样本中定位与诊断和个体化治疗开发相关的信号转导缺陷。
