Mukherji Mridul
The Skaggs Institute for Chemical Biology, Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Expert Rev Proteomics. 2005 Jan;2(1):117-28. doi: 10.1586/14789450.2.1.117.
A surprisingly fewer than expected number of genes in the human genome suggests that sophistication of its biologic system is, in part, due to complex regulation of protein activities. The activities of most cellular proteins are regulated by post-translational modifications. One of the most important post-translational modifications is reversible protein phosphorylation, which decorates more than 30% of the proteome and regulates signal transduction pathways under normal conditions as well as in disorders such as diabetes, neurodegenerative diseases, autoimmune diseases and several forms of cancers. This review examines the recent developments in mass spectrometry-based methods for phosphoproteome analysis and its applications for the study of signal transduction pathways. The basic principles of non-mass spectrometry-based methods, such as chemical genetics and flow cytometry-based approaches, are also discussed as well as their specific advantages to signaling studies. Finally, signaling pathways are discussed in the light of large-scale protein interaction studies. The proteomic methods addressed in this review are emerging as some of the essential components in systems biology, which seeks to describe signaling networks through integration of diverse types of data and, in the future, to allow computational simulations of complex biologic pathways in health and disease.
人类基因组中基因数量比预期少得出奇，这表明其生物系统的复杂性部分源于蛋白质活性的复杂调控。大多数细胞蛋白质的活性受翻译后修饰调控。最重要的翻译后修饰之一是可逆的蛋白质磷酸化，它修饰了超过30%的蛋白质组，在正常条件下以及糖尿病、神经退行性疾病、自身免疫性疾病和几种癌症等病症中调节信号转导通路。本综述探讨了基于质谱的磷酸化蛋白质组分析方法的最新进展及其在信号转导通路研究中的应用。还讨论了基于化学遗传学和基于流式细胞术等非质谱方法的基本原理，以及它们在信号研究中的特定优势。最后，根据大规模蛋白质相互作用研究对信号通路进行了讨论。本综述中涉及的蛋白质组学方法正成为系统生物学的一些重要组成部分，系统生物学旨在通过整合不同类型的数据来描述信号网络，并在未来实现对健康和疾病中复杂生物途径的计算模拟。
