University of Tokyo, Department of Mathematical Informatics, Tokyo, Japan.
IET Syst Biol. 2012 Feb;6(1):9-21. doi: 10.1049/iet-syb.2011.0016.
In this study, the author considers the design rule of the intracellular signalling pathway. In yeast pheromone signalling pathway, scaffold Ste5 tethers the components of signalling pathway, Ste11, Ste7 and Fus3. Even though scaffold complex is independently produced before stimuli, excessively expressed Fus3 as compared with scaffold exists in cytoplasm as free kinase. How the ratio of scaffold complex to the free Fus3 is determined is not clear yet. First, the contribution of free Fus3 to signal transduction is theoretically shown by using a simplified model of pheromone signalling pathway. Next, the optimum expression levels of Ste5, Ste11, Ste7 and Fus3 are systematically explored by using the detailed model and genetic algorithm under the constraint that the total expression level of these four genes is limited. Excessive expression of Fus3 is advantageous for the efficient signalling without stall of the signal transduction. The result suggests that the component of signalling pathway is optimally expressed to maximise the accumulation of phosphorylated Fus3 at a fixed time point under the constraint that the total gene expression is limited. The proposed model provides further insight into the signalling network from the point of view of not only its function but also its optimality.
在这项研究中，作者考虑了细胞内信号通路的设计规则。在酵母信息素信号通路中，支架 Ste5 将信号通路的组件 Ste11、Ste7 和 Fus3 连接在一起。尽管支架复合物在刺激之前是独立产生的，但与支架相比，过量表达的 Fus3 以游离激酶的形式存在于细胞质中。支架复合物与游离 Fus3 的比例如何确定尚不清楚。首先，通过使用简化的信息素信号通路模型，从理论上展示了游离 Fus3 对信号转导的贡献。然后，在这四个基因的总表达水平受到限制的约束下，使用详细模型和遗传算法系统地探索了 Ste5、Ste11、Ste7 和 Fus3 的最佳表达水平。过量表达 Fus3 有利于信号的有效传递，而不会使信号转导停滞。结果表明，在总基因表达受限的约束下，为了在固定时间点使磷酸化 Fus3 的积累最大化，信号通路的组成部分被最佳表达。该模型不仅从功能角度，而且从最优性角度为信号网络提供了更深入的见解。
