Mixed mechanisms of multi-site phosphorylation

Mixed mechanisms of multi-site phosphorylation
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多位点磷酸化的混合机制

DOI:
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发表时间:
2015
影响因子:
3.9
通讯作者:
J. Krishnan
J. Krishnan
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Thapanar Suwanmajo;J. Krishnan

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多位点磷酸化在细胞生物学中普遍存在,并在实验和理论上得到了广泛的研究。潜在的化学修饰机制通常被认为是分布式或过程性的。在这篇文章中,我们研究了由于磷酸化和去磷酸化涉及不同的机制,或者因为磷酸化和/或去磷酸化可以通过组合的机制发生而产生的混合机制的行为。我们研究了一系列模型,通过不同的混合机制,使用模拟、分歧分析和分析工作来评估化学信息处理。我们展示了混合机制如何显示出与纯分配和过程机制的重要和非直观的差异,在某些情况下导致具有简单剂量-反应行为的单稳态行为,而在其他情况下产生新的类似行为的振荡。我们的结果还表明,随着修饰位点数量的增加,信息处理的模式是相关的。总体而言,我们的工作创建了一个框架,以检查由于多位点修饰机制的复杂性及其对信号转导的影响而产生的信息处理。
Multi-site phosphorylation is ubiquitous in cell biology and has been widely studied experimentally and theoretically. The underlying chemical modification mechanisms are typically assumed to be distributive or processive. In this paper, we study the behaviour of mixed mechanisms that can arise either because phosphorylation and dephosphorylation involve different mechanisms or because phosphorylation and/or dephosphorylation can occur through a combination of mechanisms. We examine a hierarchy of models to assess chemical information processing through different mixed mechanisms, using simulations, bifurcation analysis and analytical work. We demonstrate how mixed mechanisms can show important and unintuitive differences from pure distributive and processive mechanisms, in some cases resulting in monostable behaviour with simple dose–response behaviour, while in other cases generating new behaviour-like oscillations. Our results also suggest patterns of information processing that are relevant as the number of modification sites increases. Overall, our work creates a framework to examine information processing arising from complexities of multi-site modification mechanisms and their impact on signal transduction.
DOI: 10.1016/j.jtbi.2011.11.014
发表时间: 2012-02-21
影响因子: 2
作者:
Kocieniewski, Pawel;Faeder, James R.;Lipniacki, Tomasz
通讯作者: Lipniacki, Tomasz
DOI: 10.1146/annurev.physchem.012809.103457
发表时间: 2010
影响因子: 14.7
作者:
Tyson JJ;Novák B
通讯作者: Novák B