Re-Writing HIStory: Identification and characterisation of the histidine phosphoproteome

磷酸的添加（磷酸化）是调节细胞内蛋白质功能的一种编码形式。细菌和酵母菌中含有的蛋白质在特定的环境变化下会磷酸化组氨酸。这种磷酸化事件对这些生物适应环境变化和生存至关重要。我们目前对人类和其他哺乳动物的组氨酸磷酸化所知甚少，因为研究它们的技术仍处于起步阶段。然而，有证据表明，哺乳动物蛋白质的组氨酸磷酸化可能参与将细胞外环境的信息传递到细胞内部，从而促进细胞反应。因此，人体组氨酸的磷酸化似乎在免疫系统和控制细胞生长速率中起作用。这些功能影响在医学上可能特别重要，因为已知异常磷酸化在癌症和糖尿病等疾病中很重要。曼彻斯特大学的克莱尔·埃耶斯博士正在开发一种策略，利用最先进的质谱仪器，在全球范围内确定组氨酸磷酸化的位点。使用这些大规模的“蛋白质组学”研究来破译组氨酸磷酸化代码对于理解这种蛋白质修饰在人类中的实际作用至关重要。在这些研究过程中，含磷酸组氨酸的蛋白质将被识别并详细表征，以确定这种修饰在调节蛋白质功能中的具体作用。重要的是，这种方法的发展和从这些研究中产生的数据将为进一步的详细分析开辟重要的领域。Eyers博士预测，组氨酸磷酸化将改变许多蛋白质的生物学功能，如果组氨酸磷酸化被证明与一种或多种疾病状态相关，她的团队将在开发和验证新的疾病靶点方面处于有利地位。

The addition of phosphate (phosphorylation) is a form of code that regulates protein function within cells. Bacteria and yeast contain proteins that are phosphorylated on the amino acid histidine in response to defined environmental changes. This phosphorylation event is critical to allow these organisms to adapt to environmental changes and survive. We currently know very little about histidine phosphorylation in humans and other mammals because the techniques to study them are still in their infancy. However there is evidence that histidine phosphorylation of mammalian proteins may be involved in transferring information about the extracellular environment to the inside of a cell, promoting a cellular response. Phosphorylation of histidine in humans thus appears to have roles in the immune system and in controlling the rate of cell growth. These functional effects could be particularly important medically, because abnormal phosphorylation is already known to be important in diseases such as cancer and diabetes. Dr Claire Eyers at the University of Manchester is developing strategies to identify sites of histidine phosphorylation on a global scale, using state-of-the-art mass spectrometry instrumentation. Deciphering the histidine phosphorylation code using these large-scale 'proteomic' studies will be crucial for understanding what this protein modification actually does in humans. During the course of these studies histidine phosphate containing proteins will be identified and then characterized in detail to assign specific roles for this modification in regulating protein function. Importantly, the development of this methodology and the generation of data from these studies will open the field significantly for further detailed analysis. Dr Eyers predicts that histidine phosphorylation will change the biological function of many proteins, and if histidine phosphorylation is shown to be correlated with one or more disease states, her group will be in a strong position to develop and validate novel disease targets.