Quantitative analysis of intracellular communication and signaling errors in signaling networks.
Quantitative analysis of intracellular communication and signaling errors in signaling networks.
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DOI：
10.1186/s12918-014-0089-z
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发表时间：
2014-08-13
影响因子：
--
通讯作者：
Abdi A
中科院分区：
文献类型：
--
作者：
Habibi I;Emamian ES;Abdi A
细胞内信号网络通过生物化学相互作用将信号从细胞膜传递到细胞核。目的是调节一些靶分子，以适当地控制细胞功能。靶分子的调节通过几种中间分子的通讯发生，所述中间分子将源自细胞膜的特异性信号传递到特异性靶输出。在这项研究中，我们提出了细胞内的信号网络模型的通信渠道。我们定义了细胞内信号网络的传输误差和信号容量的基本概念，并设计了适当的方法来计算这些参数。所开发的系统方法定量地显示了配体在结合时提供的信号如何在病理信号传导网络中丢失，这是由于一些功能失调的分子的存在。我们表明，丢失的信号导致消息传输错误，即，在网络输出处对靶蛋白的不正确调节。此外，我们展示了功能失调的分子如何影响信号网络的信号能力，以及如何计算信号分子对信号能力和信号错误的贡献。所提出的方法可以量化功能失调的信号分子在病理学发展中的作用。我们目前的实验数据，半胱天冬酶3和T细胞信号网络，以证明开发的方法及其预测的生物相关性。本研究演示了如何在病理信号网络中的信号传输和失真可以建模和研究使用所提出的方法。新方法确定了网络中分子的功能性可以影响信号传输和末端分子（如转录因子）的调节。这可以导致在信号转导网络中识别新的关键分子。这些关键分子的功能障碍可能与一些复杂的人类疾病有关。这些关键分子有可能成为药物发现的合适靶点。
Intracellular signaling networks transmit signals from the cell membrane to the nucleus, via biochemical interactions. The goal is to regulate some target molecules, to properly control the cell function. Regulation of the target molecules occurs through the communication of several intermediate molecules that convey specific signals originated from the cell membrane to the specific target outputs. In this study we propose to model intracellular signaling network as communication channels. We define the fundamental concepts of transmission error and signaling capacity for intracellular signaling networks, and devise proper methods for computing these parameters. The developed systematic methodology quantitatively shows how the signals that ligands provide upon binding can be lost in a pathological signaling network, due to the presence of some dysfunctional molecules. We show the lost signals result in message transmission error, i.e., incorrect regulation of target proteins at the network output. Furthermore, we show how dysfunctional molecules affect the signaling capacity of signaling networks and how the contributions of signaling molecules to the signaling capacity and signaling errors can be computed. The proposed approach can quantify the role of dysfunctional signaling molecules in the development of the pathology. We present experimental data on caspese3 and T cell signaling networks to demonstrate the biological relevance of the developed method and its predictions. This study demonstrates how signal transmission and distortion in pathological signaling networks can be modeled and studied using the proposed methodology. The new methodology determines how much the functionality of molecules in a network can affect the signal transmission and regulation of the end molecules such as transcription factors. This can lead to the identification of novel critical molecules in signal transduction networks. Dysfunction of these critical molecules is likely to be associated with some complex human disorders. Such critical molecules have the potential to serve as proper targets for drug discovery.
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影响因子：
4.3
作者：
Saez-Rodriguez J;Simeoni L;Lindquist JA;Hemenway R;Bommhardt U;Arndt B;Haus UU;Weismantel R;Gilles ED;Klamt S;Schraven B
通讯作者：
Schraven B
DOI：
10.1186/1478-811x-11-43
发表时间：
2013-06-26
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Samaga R;Klamt S
通讯作者：
Klamt S
影响因子：
7.3
作者：
Abdi, Ali;Tahoori, Mehdi Baradaran;Emamian, Effat S.
通讯作者：
Emamian, Effat S.
影响因子：
3.5
作者：
Cha, Young;Park, Kyung-Soon
通讯作者：
Park, Kyung-Soon
影响因子：
30.8
作者：
Emamian, ES;Hall, D;Gogos, JA
通讯作者：
Gogos, JA