Dynamics and control of the ERK signaling pathway: Sensitivity, bistability, and oscillations.
Dynamics and control of the ERK signaling pathway: Sensitivity, bistability, and oscillations.
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DOI：
10.1371/journal.pone.0195513
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Yasemi M
中科院分区：
文献类型：
--
作者：
Arkun Y;Yasemi M
细胞信号传导是细胞外信息传递到细胞内以执行有用的生物功能的过程。ERK信号通路控制着细胞的生长、增殖、分化和凋亡等过程。在这项工作中考虑的ERK信号通路开始于细胞外刺激，结束于活化的（双磷酸化的）ERK，其被易位到细胞核中。我们通过将其分解为三个功能子系统来建模和分析这个复杂的途径。第一个子系统跨越从细胞外生长因子到SOS复合物ShC-Grb 2-SOS形成的途径的初始部分。第二个子系统包括由SOS复合物介导的Ras的激活。随后是MAPK子系统（或Raf-MEK-ERK途径），其在被Ras激活后产生双磷酸化ERK。虽然单独的模型存在于文献中的子系统水平，一个完整的系统，包括重要的监管反馈回路的综合模型是失踪。我们的动态模型结合了现有的子系统模型，并研究了它们在反馈下的稳态和动态相互作用。我们建立的条件下，双稳态和振荡存在这一重要途径。特别是，我们展示了负反馈和正反馈回路如何影响决定细胞结果的动态特性。
Cell signaling is the process by which extracellular information is transmitted into the cell to perform useful biological functions. The ERK (extracellular-signal-regulated kinase) signaling controls several cellular processes such as cell growth, proliferation, differentiation and apoptosis. The ERK signaling pathway considered in this work starts with an extracellular stimulus and ends with activated (double phosphorylated) ERK which gets translocated into the nucleus. We model and analyze this complex pathway by decomposing it into three functional subsystems. The first subsystem spans the initial part of the pathway from the extracellular growth factor to the formation of the SOS complex, ShC-Grb2-SOS. The second subsystem includes the activation of Ras which is mediated by the SOS complex. This is followed by the MAPK subsystem (or the Raf-MEK-ERK pathway) which produces the double phosphorylated ERK upon being activated by Ras. Although separate models exist in the literature at the subsystems level, a comprehensive model for the complete system including the important regulatory feedback loops is missing. Our dynamic model combines the existing subsystem models and studies their steady-state and dynamic interactions under feedback. We establish conditions under which bistability and oscillations exist for this important pathway. In particular, we show how the negative and positive feedback loops affect the dynamic characteristics that determine the cellular outcome.
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影响因子：
64.8
作者：
Barkai, N;Leibler, S
通讯作者：
Leibler, S
影响因子：
4.3
作者：
Kawashima, Nagako;Nakayama, Kenichi;Biju, Vasudevanpillai
通讯作者：
Biju, Vasudevanpillai
DOI：
10.1046/j.1432-1327.2000.01197.x
发表时间：
2000-03-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Kholodenko, BN
通讯作者：
Kholodenko, BN
影响因子：
64.5
作者：
Das J;Ho M;Zikherman J;Govern C;Yang M;Weiss A;Chakraborty AK;Roose JP
通讯作者：
Roose JP
影响因子：
4.1
作者：
Hatakeyama, M;Kimura, S;Konagaya, A
通讯作者：
Konagaya, A