Burton Jeremy C, Royer Fredejah, Grimsey Neil J
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia Athens, Athens, Georgia, USA.
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia Athens, Athens, Georgia, USA.
J Biol Chem. 2024 Nov;300(11):107846. doi: 10.1016/j.jbc.2024.107846. Epub 2024 Oct 1.
The delicate balance of cell physiology is implicitly tied to the expression and activation of proteins. Post-translational modifications offer a tool to dynamically switch protein activity on and off to orchestrate a wide range of protein-protein interactions to tune signal transduction during cellular homeostasis and pathological responses. There is a growing acknowledgment that subcellular locations of kinases define the spatial network of potential scaffolds, adaptors, and substrates. These highly ordered and localized biomolecular microdomains confer a spatially distinct bias in the outcomes of kinase activity. Furthermore, they may hold essential clues to the underlying mechanisms that promote disease. Developing tools to dissect the spatiotemporal activation of kinases is critical to reveal these mechanisms and promote the development of spatially targeted kinase inhibitors. Here, we discuss the spatial regulation of kinases, the tools used to detect their activity, and their potential impact on human health.
细胞生理学的微妙平衡与蛋白质的表达和激活密切相关。翻译后修饰提供了一种工具，可动态地开启和关闭蛋白质活性，以协调广泛的蛋白质-蛋白质相互作用，从而在细胞稳态和病理反应过程中调节信号转导。越来越多的人认识到，激酶的亚细胞定位定义了潜在支架、衔接蛋白和底物的空间网络。这些高度有序且局部化的生物分子微结构域在激酶活性的结果中赋予了空间上独特的偏向性。此外，它们可能为促进疾病发生的潜在机制提供关键线索。开发剖析激酶时空激活的工具对于揭示这些机制以及促进空间靶向激酶抑制剂的开发至关重要。在此，我们讨论激酶的空间调控、用于检测其活性的工具及其对人类健康的潜在影响。
