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蛋白磷酸酶的信号转导与药物研发:以系统为中心的观点。

Signalling by protein phosphatases and drug development: a systems-centred view.

机构信息

Systems Biology Ireland, University College Dublin, Belfield, Ireland.

出版信息

FEBS J. 2013 Jan;280(2):751-65. doi: 10.1111/j.1742-4658.2012.08522.x. Epub 2012 Mar 14.

DOI:10.1111/j.1742-4658.2012.08522.x
PMID:22340367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3368988/
Abstract

Protein modification cycles catalysed by opposing enzymes, such as kinases and phosphatases, form the backbone of signalling networks. Although, historically, kinases have been at the research forefront, a systems-centred approach reveals predominant roles for phosphatases in controlling the network response times and spatio-temporal profiles of signalling activities. Emerging evidence suggests that phosphatase kinetics are critical for network function and cell-fate decisions. Protein phosphatases operate as both immediate and delayed regulators of signal transduction, capable of attenuating or amplifying signalling. This versatility of phosphatase action emphasizes the need for systems biology approaches to understand cellular signalling networks and predict the cellular outcomes of combinatorial drug interventions.

摘要

由相对酶(如激酶和磷酸酶)催化的蛋白质修饰循环构成了信号网络的主干。尽管激酶在历史上一直处于研究前沿,但以系统为中心的方法表明,磷酸酶在控制网络响应时间和信号活动的时空特征方面起着主要作用。新出现的证据表明,磷酸酶动力学对于网络功能和细胞命运决策至关重要。蛋白磷酸酶既是信号转导的即时调节因子,也是延迟调节因子,能够减弱或增强信号。磷酸酶作用的这种多功能性强调了需要采用系统生物学方法来理解细胞信号网络,并预测组合药物干预的细胞结果。

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