Three-state kinetic mechanism for scaffold-mediated signal transduction.
Three-state kinetic mechanism for scaffold-mediated signal transduction.
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支架介导的信号转导的三态动力学机制。
DOI：
10.1103/physreve.78.051921
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Locasale,JasonW
中科院分区：
文献类型：
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作者：
Locasale,JasonW
真核细胞中的信号传导事件通常由支架蛋白引导。支架蛋白将多种蛋白质组装成空间定位的信号复合物，并对信号通路产生多种物理效应。为了研究这些效应，我们考虑了支架介导的激酶激活的最小三态动力学模型。我们首先引入并应用路径求和技术来获得控制蛋白激酶激活的单分子主方程的近似解。然后我们考虑精确的数值解。我们评论这种近似何时合适，然后使用此分析来说明在支架蛋白存在的情况下参与信号转导的多个时间尺度上发生的过程的竞争。我们发现我们的最小模型捕获了支架浓度如何影响信号在激酶级联中分布的时间。对于一系列支架浓度，支架允许信号分布数十年。研究结果与最近的实验和模拟数据一致。这些结果提供了一个框架和机制，用于理解支架蛋白如何影响激酶激活的等待时间分布的形状，并有效地延长细胞信号传导过程中蛋白激酶被激活的时间。
Signaling events in eukaryotic cells are often guided by a scaffolding protein. Scaffold proteins assemble multiple proteins into a spatially localized signaling complex and exert numerous physical effects on signaling pathways. To study these effects, we consider a minimal, three-state kinetic model of scaffold-mediated kinase activation. We first introduce and apply a path summation technique to obtain approximate solutions to a single molecule master equation that governs protein kinase activation. We then consider exact numerical solutions. We comment on when this approximation is appropriate and then use this analysis to illustrate the competition of processes occurring at many time scales that are involved in signal transduction in the presence of a scaffold protein. We find that our minimal model captures how scaffold concentration can influence the times over which signaling is distributed in kinase cascades. For a range of scaffold concentrations, scaffolds allow for signaling to be distributed over multiple decades. The findings are consistent with recent experiments and simulation data. These results provide a framework and offer a mechanism for understanding how scaffold proteins can influence the shape of the waiting time distribution of kinase activation and effectively broaden the times over which protein kinases are activated in the course of cell signaling.