MAP kinase modules: the excursion model and the steps that count.
MAP kinase modules: the excursion model and the steps that count.
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DOI：
10.1016/j.bpj.2014.09.024
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发表时间：
2014-11
影响因子：
3.4
通讯作者：
A. Piala;J. Humphreys;E. Goldsmith
中科院分区：
文献类型：
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作者：
A. Piala;J. Humphreys;E. Goldsmith
MAP激酶模块将不同的细胞外信号传播到下游效应器。由模块催化的两个双重磷酸化反应被认为控制通路的开关行为。在这里，我们回顾了最近的方法来了解这些途径，通过在细胞和体外的信号响应研究。这些数据与物理模型以及数学和理论基础上的预测相一致。最近的生化分析表明，由MAP激酶模块催化的双重磷酸化反应在级联反应的两个水平上是连续的。所观察到的磷酸化事件的顺序表明从MAP 3 K的Ser/Thr激酶活性偏移到中心双重特异性MAP 2K的Tyr激酶活性。讨论了事件的顺序如何在结构和相互作用中编码。有序的机制证实了反应应该是顺序的预测，以产生陡峭的信号-响应曲线和细胞中观察到的延迟响应。
MAP kinase modules propagate diverse extracellular signals to downstream effectors. The two dual phosphorylation reactions catalyzed by the modules are thought to control the switch behavior of the pathway. Here we review recent approaches to understand these pathways through signal-to-response studies in cells and in vitro. These data are reconciled with physical models as well as predictions made on mathematical and theoretical grounds. Biochemical analysis has shown recently that the dual phosphorylation reactions catalyzed by MAP kinase modules are sequential at both levels of the cascade. The observed order of phosphorylation events suggests an excursion from the Ser/Thr kinase activity of the MAP3K into Tyr kinase activity of the central dual specificity MAP2K. How the order of events might be encoded in the structures and interactions is discussed. The ordered mechanism confirms predictions that reactions should be sequential to generate the steep signal-to-response curves and delayed responses observed in cells.