Vyse Simon, Desmond Howard, Huang Paul H
Division of Cancer Biology, The Institute of Cancer Research , London SW3 6JB, England.
IUCrJ. 2017 Feb 23;4(Pt 2):119-130. doi: 10.1107/S2052252516020546. eCollection 2017 Mar 1.
Receptor tyrosine kinases (RTKs) are key transmembrane environmental sensors that are capable of transmitting extracellular information into phenotypic responses, including cell proliferation, survival and metabolism. Advances in mass spectrometry (MS)-based phosphoproteomics have been instrumental in providing the foundations of much of our current understanding of RTK signalling networks and activation dynamics. Furthermore, new insights relating to the deregulation of RTKs in disease, for instance receptor co-activation and kinome reprogramming, have largely been identified using phosphoproteomic-based strategies. This review outlines the current approaches employed in phosphoproteomic workflows, including phosphopeptide enrichment and MS data-acquisition methods. Here, recent advances in the application of MS-based phosphoproteomics to bridge critical gaps in our knowledge of RTK signalling are focused on. The current limitations of the technology are discussed and emerging areas such as computational modelling, high-throughput phospho-proteomic workflows and next-generation single-cell approaches to further our understanding in new areas of RTK biology are highlighted.
受体酪氨酸激酶（RTK）是关键的跨膜环境传感器，能够将细胞外信息转化为表型反应，包括细胞增殖、存活和代谢。基于质谱（MS）的磷酸化蛋白质组学的进展为我们目前对RTK信号网络和激活动力学的大部分理解奠定了基础。此外，与疾病中RTK失调相关的新见解，如受体共激活和激酶组重编程，很大程度上是通过基于磷酸化蛋白质组学的策略确定的。本综述概述了磷酸化蛋白质组学工作流程中使用的当前方法，包括磷酸肽富集和MS数据采集方法。这里重点介绍了基于MS的磷酸化蛋白质组学应用方面的最新进展，以弥合我们在RTK信号知识方面的关键差距。讨论了该技术目前的局限性，并强调了新兴领域，如计算建模、高通量磷酸化蛋白质组学工作流程和下一代单细胞方法，以加深我们对RTK生物学新领域的理解。
