Specificity and robustness of the mammalian MAPK-IEG network.
Specificity and robustness of the mammalian MAPK-IEG network.
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DOI：
10.1016/j.bpj.2008.10.076
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发表时间：
2009-05
影响因子：
3.4
通讯作者：
Craig J. Thalhauser;N. Komarova
中科院分区：
文献类型：
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作者：
Craig J. Thalhauser;N. Komarova
丝裂原活化蛋白激酶级联是一种保守的信号转导途径，存在于从酵母到人类的复杂生物体中。在许多哺乳动物组织类型中，该途径可以正确地识别来自不同细胞外信使的信号，导致特异性且通常相互排斥的细胞反应。转导的信号通过一套复杂的正反馈和负反馈控制机制进行调节，并输入下游基因表达网络。这个网络，基于即时早期基因系统，有两种可能的，相互排斥的结果。利用数学模型，我们研究了不同的刺激如何导致不同的时间信号结构。此外，我们研究了每个反馈控制如何有助于基因表达输出的整体特异性，并假设哺乳动物促分裂原活化蛋白激酶途径的复杂性质导致系统能够稳健地识别和识别适当的信号，而无需投资于两个完全独立的信号级联。最后，我们量化了RKIP蛋白在塑造信号中的作用，并提出了其参与癌症转移的新机制。
The mitogen-activated protein kinase cascade is a conserved signal transduction pathway found in organisms of complexity spanning from yeast to humans. In many mammalian tissue types, this pathway can correctly transduce signals from different extracellular messengers, leading to specific and often mutually exclusive cellular responses. The transduced signal is tuned by a complicated set of positive and negative feedback control mechanisms and fed into a downstream gene expression network. This network, based on the immediate early gene system, has two possible, mutually exclusive outcomes. Using a mathematical model, we study how different stimuli lead to different temporal signal structure. Further, we investigate how each of the feedback controls contributes to the overall specificity of the gene expression output, and hypothesize that the complicated nature of the mammalian mitogen-activated protein kinase pathway results in a system able to robustly identify and transduce the proper signal without investing in two completely separate signal cascades. Finally, we quantify the role of the RKIP protein in shaping the signal, and propose a novel mechanism of its involvement in cancer metastasis.