Sadreev Ildar I, Chen Michael Z Q, Welsh Gavin I, Umezawa Yoshinori, Kotov Nikolay V, Valeyev Najl V
Centre for Systems, Dynamics and Control, College of Engineering, Mathematics and Physical Sciences, University of Exeter, Harrison Building, Exeter, United Kingdom.
Department of Mechanical Engineering, The University of Hong Kong, Hong Kong, China.
PLoS One. 2014 Oct 21;9(10):e110913. doi: 10.1371/journal.pone.0110913. eCollection 2014.
Phosphorylation is a fundamental biochemical reaction that modulates protein activity in cells. While a single phosphorylation event is relatively easy to understand, multisite phosphorylation requires systems approaches for deeper elucidation of the underlying molecular mechanisms. In this paper we develop a mechanistic model for single- and multi-site phosphorylation. The proposed model is compared with previously reported studies. We compare the predictions of our model with experiments published in the literature in the context of inflammatory signaling events in order to provide a mechanistic description of the multisite phosphorylation-mediated regulation of Signal Transducer and Activator of Transcription 3 (STAT3) and Interferon Regulatory Factor 5 (IRF-5) proteins. The presented model makes crucial predictions for transcription factor phosphorylation events in the immune system. The model proposes potential mechanisms for T cell phenotype switching and production of cytokines. This study also provides a generic framework for the better understanding of a large number of multisite phosphorylation-regulated biochemical circuits.
磷酸化是一种基本的生化反应，可调节细胞中的蛋白质活性。虽然单个磷酸化事件相对容易理解，但多位点磷酸化需要采用系统方法才能更深入地阐明其潜在的分子机制。在本文中，我们开发了一个用于单位点和多位点磷酸化的机制模型。将所提出的模型与先前报道的研究进行了比较。我们将模型的预测结果与文献中发表的关于炎症信号事件的实验进行比较，以便对多位点磷酸化介导的信号转导和转录激活因子3（STAT3）及干扰素调节因子5（IRF-5）蛋白的调控提供一个机制性描述。所展示的模型对免疫系统中的转录因子磷酸化事件做出了关键预测。该模型提出了T细胞表型转换和细胞因子产生的潜在机制。这项研究还为更好地理解大量受多位点磷酸化调节的生化回路提供了一个通用框架。
