Mettetal Jerome T, Muzzey Dale, Gómez-Uribe Carlos, van Oudenaarden Alexander
Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science. 2008 Jan 25;319(5862):482-4. doi: 10.1126/science.1151582.
The propagation of information through signaling cascades spans a wide range of time scales, including the rapid ligand-receptor interaction and the much slower response of downstream gene expression. To determine which dynamic range dominates a response, we used periodic stimuli to measure the frequency dependence of signal transduction in the osmo-adaptation pathway of Saccharomyces cerevisiae. We applied system identification methods to infer a concise predictive model. We found that the dynamics of the osmo-adaptation response are dominated by a fast-acting negative feedback through the kinase Hog1 that does not require protein synthesis. After large osmotic shocks, an additional, much slower, negative feedback through gene expression allows cells to respond faster to future stimuli.
信息通过信号级联的传播跨越了广泛的时间尺度，包括快速的配体-受体相互作用以及下游基因表达的慢得多的响应。为了确定哪个动态范围主导响应，我们使用周期性刺激来测量酿酒酵母渗透适应途径中信号转导的频率依赖性。我们应用系统识别方法来推断一个简洁的预测模型。我们发现，渗透适应反应的动力学由通过激酶Hog1的快速作用负反馈主导，这一过程不需要蛋白质合成。在受到大的渗透压冲击后，通过基因表达的另一个慢得多的负反馈使细胞能够对未来的刺激做出更快的反应。
