English Justin G, Shellhammer James P, Malahe Michael, McCarter Patrick C, Elston Timothy C, Dohlman Henrik G
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Mathematics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Sci Signal. 2015 Jan 13;8(359):ra5. doi: 10.1126/scisignal.2005774.
Signaling pathways can behave as switches or rheostats, generating binary or graded responses to a given cell stimulus. We evaluated whether a single signaling pathway can simultaneously encode a switch and a rheostat. We found that the kinase Hog1 mediated a bifurcated cellular response: Activation and commitment to adaptation to osmotic stress are switchlike, whereas protein induction and the resolution of this commitment are graded. Through experimentation, bioinformatics analysis, and computational modeling, we determined that graded recovery is encoded through feedback phosphorylation and a gene induction program that is both temporally staggered and variable across the population. This switch-to-rheostat signaling mechanism represents a versatile stress adaptation system, wherein a broad range of inputs generate an "all-in" response that is later tuned to allow graded recovery of individual cells over time.
信号通路可起到开关或变阻器的作用，对给定的细胞刺激产生二元或分级反应。我们评估了单一信号通路是否能同时编码开关和变阻器。我们发现激酶Hog1介导了一种分支细胞反应：激活并致力于适应渗透胁迫是类似开关的，而蛋白质诱导和这种反应的消退是分级的。通过实验、生物信息学分析和计算建模，我们确定分级恢复是通过反馈磷酸化和一个在时间上交错且在群体中可变的基因诱导程序来编码的。这种从开关到变阻器的信号机制代表了一种通用的应激适应系统，其中广泛的输入产生一种“全力以赴”的反应，随后进行调整以允许单个细胞随时间进行分级恢复。
