Mathematical models of protein kinase signal transduction
Mathematical models of protein kinase signal transduction
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DOI：
10.1016/s1097-2765(02)00528-2
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发表时间：
2002-05-01
期刊：
影响因子：
16
通讯作者：
Rapoport, TA
中科院分区：
文献类型：
--
作者：
Heinrich, R;Neel, BG;Rapoport, TA
我们已经开发了一个数学理论，它描述了作为有限数量的关键参数的函数的信号通路的调节。我们的分析包括线性激酶-磷酸酶级联反应，以及包含反馈相互作用，与其他信号通路的串扰和/或支架和G蛋白的系统。我们发现，磷酸酶有一个更显着的效果比激酶的速率和持续时间的信号，而信号幅度主要是由激酶控制。最简单的模型通路允许放大的信号仅以缓慢的信号传播为代价。更复杂和现实的途径可以将联合收割机高扩增和信号速率与稳定关闭状态的维持相结合。我们的模型还解释了不同的激动剂如何引起相同通路的瞬时或持续信号传导，并为信号通路设计提供了理论基础。
We have developed a mathematical theory that describes the regulation of signaling pathways as a function of a limited number of key parameters. Our analysis includes linear kinase-phosphatase cascades, as well as systems containing feedback interactions, crosstalk with other signaling pathways, and/or scaffolding and G proteins. We find that phosphatases have a more pronounced effect than kinases on the rate and duration of signaling, whereas signal amplitude is controlled primarily by kinases. The simplest model pathways allow amplified signaling only at the expense of slow signal propagation. More complex and realistic pathways can combine high amplification and signaling rates with maintenance of a stable off state. Our models also explain how different agonists can evoke transient or sustained signaling of the same pathway and provide a rationale for signaling pathway design.