Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
Cell. 2014 Feb 27;156(5):1084-95. doi: 10.1016/j.cell.2014.01.013.
Cells continuously adjust their behavior in response to changing environmental conditions. Both intensity and duration of external signals are critical factors in determining what response is initiated. To understand how intracellular signaling networks process such multidimensional information, we studied the AtRGS1-mediated glucose response system of Arabidopsis. By combining experiments with mathematical modeling, we discovered a reciprocal dose and duration response relying on the orchestrated action of three kinases (AtWNK1, AtWNK8, and AtWNK10) acting on distinct timescales and activation thresholds. Specifically, we find that high concentrations of D-glucose rapidly signal through AtWNK8 and AtWNK10, whereas low, sustained sugar concentration slowly activate the pathway through AtWNK1, allowing the cells to respond similarly to transient, high-intensity signals and sustained, low-intensity signals. This "dose-duration reciprocity" allows encoding of both the intensity and persistence of glucose as an important energy resource and signaling molecule.
细胞不断根据环境条件的变化调整其行为。外部信号的强度和持续时间是决定启动何种反应的关键因素。为了了解细胞内信号网络如何处理这种多维信息，我们研究了拟南芥中 AtRGS1 介导的葡萄糖反应系统。通过将实验与数学建模相结合，我们发现了一种依赖于三种激酶（AtWNK1、AtWNK8 和 AtWNK10）在不同时间尺度和激活阈值上协调作用的剂量和持续时间反应。具体来说，我们发现高浓度的 D-葡萄糖通过 AtWNK8 和 AtWNK10 快速传递信号，而低浓度、持续的糖浓度则通过 AtWNK1 缓慢激活途径，使细胞能够对短暂的高强度信号和持续的低强度信号做出相似的反应。这种“剂量-持续时间相互作用”允许将葡萄糖作为重要的能量资源和信号分子的强度和持久性进行编码。
