Revealing Secrets of Cellular Phosphorylation Systems Using Mass Spectrometry

蛋白质磷酸化是一种化学修饰，被所有生物用来改变蛋白质的功能，控制细胞通讯、生长、新陈代谢、分化和生存等过程。在蛋白质中添加和移除磷酸盐分子的酶分别称为激动酶和磷酸酶。由于可逆磷酸化的微妙平衡对细胞内稳态至关重要，所有激酶/磷酸酶的活动都受到密切关注。生物质谱学是研究磷酸化体系的最有力的分析工具之一。基于质谱学的方法可以快速鉴定含有激酶和磷酸酶的功能多蛋白复合体，并直接定位磷酸盐加成的位置，以便更好地研究蛋白质修饰的后果。因此，我们研究计划的长期目标是整合质谱学、生物化学和细胞生物学技术，以破译调控鲜为人知的激酶和磷酸酶的机制细节，预计这些酶和磷酸酶将调控基本的细胞过程。

Protein phosphorylation is a chemical modification utilized by all living organisms to alter the function of proteins and controls processes such as cellular communication, growth, metabolism, differentiation, and survival. The enzymes that add and remove phosphate molecules to proteins are called kinases and phosphatases respectively.  Since a delicate balance of reversible phosphorylation is essential for cellular homeostasis, the actions of all kinases/phosphatases are under tight surveillance. One of the most powerful analytical tools to study phosphorylation systems is biological mass spectrometry. Mass spectrometry based methods can rapidly identify functional multiprotein complexes containing kinases and phosphatases as well as directly map the location of phosphate addition to better study the consequence of the protein modification. Accordingly, the long term goal of our research program is to integrate mass spectrometry, biochemistry, and cell biology techniques to decipher the mechanistic details regulating poorly understood kinases and phosphatases predicted to regulate fundamental cellular processes.