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

磷酸盐的添加（磷酸化）是一种调节细胞内蛋白质功能的密码形式。细菌和酵母含有蛋白质，这些蛋白质在氨基酸组氨酸上磷酸化，以响应确定的环境变化。这种磷酸化事件对于这些生物体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知之甚少，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，促进细胞反应。因此，人类组氨酸的磷酸化似乎在免疫系统和控制细胞生长速率中发挥作用。这些功能效应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Claire Eyers博士正在开发策略，使用最先进的质谱仪器在全球范围内识别组氨酸磷酸化位点。使用这些大规模的“蛋白质组学”研究来破译组氨酸磷酸化密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，将鉴定含组氨酸磷酸的蛋白质，然后详细表征，以指定这种修饰在调节蛋白质功能中的特定作用。重要的是，这种方法的发展和这些研究产生的数据将为进一步的详细分析打开大门。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，她的团队将处于开发和验证新疾病靶点的有利地位。

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.