Spatiotemporal control of kinases and the biomolecular tools to trace activity.

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.