An Algebraic Approach to Signaling Cascades with n Layers
An Algebraic Approach to Signaling Cascades with n Layers
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DOI：
10.1007/s11538-011-9658-0
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发表时间：
2012-01-01
影响因子：
3.5
通讯作者：
Wiuf, Carsten
中科院分区：
文献类型：
--
作者：
Feliu, Elisenda;Knudsen, Michael;Wiuf, Carsten
蛋白质的翻译后修饰是细胞信号传递的关键。许多信号通路包含几层修饰循环，通过通路介导和改变信号。在这里，我们研究了一个简单的信号级联，包括n层的修饰循环，使一层的修饰蛋白质作为修饰剂在下一层。假设质量作用动力学，并考虑到中间复合物的形成，我们表明，稳定状态是一个多项式在一个变量的解决方案，事实上，有一个稳定状态的任何给定的总量的底物和enzymes.We证明，许多稳态浓度相关的合理的功能，可以递归地找到。例如，刺激-反应曲线作为显式有理函数的反函数出现。我们表明，修改后的基板的刺激响应曲线向左移动，因为我们向下移动的级联。此外，我们的方法使我们能够研究酶竞争、封存以及稳态如何响应底物总量的变化而变化。我们的方法本质上是代数的，遵循翻译后修饰系统研究的最新趋势。
Posttranslational modification of proteins is key in transmission of signals in cells. Many signaling pathways contain several layers of modification cycles that mediate and change the signal through the pathway. Here, we study a simple signaling cascade consisting of n layers of modification cycles such that the modified protein of one layer acts as modifier in the next layer. Assuming mass-action kinetics and taking the formation of intermediate complexes into account, we show that the steady states are solutions to a polynomial in one variable and in fact that there is exactly one steady state for any given total amounts of substrates and enzymes.We demonstrate that many steady-state concentrations are related through rational functions that can be found recursively. For example, stimulus-response curves arise as inverse functions to explicit rational functions. We show that the stimulus-response curves of the modified substrates are shifted to the left as we move down the cascade. Further, our approach allows us to study enzyme competition, sequestration, and how the steady state changes in response to changes in the total amount of substrates.Our approach is essentially algebraic and follows recent trends in the study of posttranslational modification systems.