Cross-talk and decision making in MAP kinase pathways
Cross-talk and decision making in MAP kinase pathways
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DOI：
10.1038/ng1957
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发表时间：
2007-03-01
期刊：
影响因子：
30.8
通讯作者：
Ramanathan, Sharad
中科院分区：
文献类型：
--
作者：
McClean, Megan N.;Mody, Areez;Ramanathan, Sharad
细胞必须对不同的环境刺激做出特异性反应才能生存。参与感知这些刺激的信号转导途径通常共享相同或同源的蛋白质。尽管有潜在的交叉连接，细胞显示出特异性的反应。我们表明，通过建模，这些途径暴露于同时和时间顺序的输入的生理反应可以证明系统级的机制，途径实现特异性。我们将这些结果应用于高渗和信息素丝裂原活化蛋白（MAP）激酶途径的酵母酿酒酵母。这两条途径特异性地感知渗透和信息素信号（1-3），尽管共享MAPKKK，Ste 11，并具有同源的MAPK（Fus 3和Hog 1）。我们发现，在单个细胞中，这些通路在一系列输入中是重叠的，即使暴露于两种刺激，细胞也只对一种刺激做出反应。我们的研究结果表明，这些途径实现的特异性过滤虚假的串扰通过相互抑制。单元之间的可变性允许决策的异质性。
Cells must respond specifically to different environmental stimuli in order to survive. The signal transduction pathways involved in sensing these stimuli often share the same or homologous proteins. Despite potential cross-wiring, cells show specificity of response. We show, through modeling, that the physiological response of such pathways exposed to simultaneous and temporally ordered inputs can demonstrate system-level mechanisms by which pathways achieve specificity. We apply these results to the hyperosmolar and pheromone mitogen-activated protein (MAP) kinase pathways in the yeast Saccharomyces cerevisiae. These two pathways specifically sense osmolar and pheromone signals(1-3), despite sharing a MAPKKK, Ste11, and having homologous MAPKs (Fus3 and Hog1). We show that in a single cell, the pathways are bistable over a range of inputs, and the cell responds to only one stimulus even when exposed to both. Our results imply that these pathways achieve specificity by filtering out spurious cross-talk through mutual inhibition. The variability between cells allows for heterogeneity of the decisions.