磷酸化蛋白质组学富集策略进展及其在疾病研究中的应用

蛋白质磷酸化是生物体内重要的翻译后修饰，几乎参与调节着细胞增殖、信号转导、新陈代谢、肿瘤发生等过程在内的所有生命活动。对磷酸化蛋白质组的全面分析可以帮助人们深入了解磷酸化蛋白在生命过程中的作用，协助发现生物标志物，辅助疾病的诊疗。然而，磷酸化蛋白丰度低、信号被非磷酸化肽段所掩盖等问题限制了磷酸化蛋白质组学的发展。因此，亟需开发高效的富集策略，如设计新型纳米材料，合并多种分析方法等，以提高检测灵敏度、富集特异性，增大富集容量。本文回顾了近年来磷酸化蛋白质组学研究策略中的富集策略进展及其在疾病研究中的应用。

Advances in enrichment strategies for phosphoproteomics and its application in the research of disease

Protein phosphorylation is one of the most common post-translational modifications(PTMs)in various organisms, which plays critical roles in the regulation of intracellular biological processes such as cell proliferation, signal transduction, metabolismics and tumorigenesis. The understanding of phosphoproteomics is playing a great role in biomarker discovery, auxiliary treatment, as well as biological process exploration. However, the identification and characterization of phosphoproteins remain challenging due to their low abundance and the signal suppression of nonphosphorylated peptides. Thus, extraction of phosphorylated polypeptides from complex mixtures is a critical step in the success of phosphoproteomics experiments. Some strategies have been explored to promote enrichment specificity, detection sensitivity and enrichment capacity, such as design of new nanomaterials or combination of a variety of analytical methods. This review places special emphasis on the recent four-year advances for enrichment strategies that have been used for phosphoproteomics and summarize the application of phosphoproteomics in disease research.