Modeling and stochastic simulation of the Ras/cAMP/PKA pathway in the yeast Saccharomyces cerevisiae evidences a key regulatory function for intracellular guanine nucleotides pools
Modeling and stochastic simulation of the Ras/cAMP/PKA pathway in the yeast Saccharomyces cerevisiae evidences a key regulatory function for intracellular guanine nucleotides pools
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DOI：
10.1016/j.jbiotec.2007.09.019
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发表时间：
2008-02-01
影响因子：
4.1
通讯作者：
Martegani, Enzo
中科院分区：
文献类型：
--
作者：
Cazzaniga, Paolo;Pescini, Dario;Martegani, Enzo
在酿酒酵母中，Ras/cAMP/PKA 途径参与代谢和细胞周期进程的调节。该途径受到多种控制机制的严格调节，因为反馈循环由磷酸二酯酶的活性控制。在这里，我们提出了 Ras/cAMP/PKA 途径的离散数学模型，该模型考虑了其主要细胞质成分及其相互相互作用。然后使用 tau 跳跃算法对模型进行随机模拟。我们在各种条件下研究该系统，并测试几个随机反应常数的不同值如何影响途径行为。最后，我们表明鸟嘌呤核苷酸、GTP 和 GDP 的水平可能是整个途径调节的相关代谢信号。 (C) 2007 Elsevier B.V. 保留所有权利。
In the yeast Saccharomyces cerevisiae, the Ras/cAMP/PKA pathway is involved in the regulation of metabolism and cell cycle progression. The pathway is tightly regulated by several control mechanisms, as the feedback cycle ruled by the activity of phosphodiesterase. Here, we present a discrete mathematical model for the Ras/cAMP/PKA pathway that considers its principal cytoplasmic components and their mutual interactions. The tau-leaping algorithm is then used to perform stochastic simulations of the model. We investigate this system under various conditions, and we test how different values of several stochastic reaction constants affect the pathway behaviour. Finally, we show that the level of guanine nucleotides, GTP and GDP, could be relevant metabolic signals for the regulation of the whole pathway. (C) 2007 Elsevier B.V. All rights reserved.