Mathematical models of specifcity in cell signaling
Mathematical models of specifcity in cell signaling
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DOI：
10.1529/biophysj.106.090084
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发表时间：
2007-05-10
影响因子：
3.4
通讯作者：
Komarova, Natalia L.
中科院分区：
文献类型：
--
作者：
Bardwell, Lee;Zou, Xiufen;Komarova, Natalia L.
细胞信号传导途径将细胞外信号转化为适当的反应。这些途径通常相互连接形成网络，通常具有共享相似或相同组件的不同途径。这种连通性的后果是潜在的串扰，其中一些可能是不希望的。事实上，实验证据表明，细胞已经进化出绝缘机制，以部分抑制通路之间的“泄漏”。在这里，我们描述了简单的信号网络的数学模型，并获得准确的分析表达式的两个措施的串扰称为特异性和保真度。几个绝缘机制的性能-组合信号，区室化，抑制一个途径的另一个，和支架蛋白的选择性激活-相对于它们提供的特异性和它们放置在网络上的约束之间的权衡进行评估。噪声的影响也进行了研究。从这种分析中获得的见解适用于了解酵母交配和侵入性生长MAP激酶信号网络的特异性。
Cellular signaling pathways transduce extracellular signals into appropriate responses. These pathways are typically interconnected to form networks, often with different pathways sharing similar or identical components. A consequence of this connectedness is the potential for cross talk, some of which may be undesirable. Indeed, experimental evidence indicates that cells have evolved insulating mechanisms to partially suppress "leaking'' between pathways. Here we characterize mathematical models of simple signaling networks and obtain exact analytical expressions for two measures of cross talk called specificity and fidelity. The performance of several insulating mechanisms - combinatorial signaling, compartmentalization, the inhibition of one pathway by another, and the selective activation of scaffold proteins - is evaluated with respect to the trade-off between the specificity they provide and the constraints they place on the network. The effects of noise are also examined. The insights gained from this analysis are applied to understanding specificity in the yeast mating and invasive growth MAP kinase signaling network.