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通过爆发性钙振荡对蛋白质进行差异调节——一项理论研究

Differential regulation of proteins by bursting calcium oscillations--a theoretical study.

作者信息

Schuster Stefan, Knoke Beate, Marhl Marko

机构信息

Department of Bioinformatics, Faculty of Biology and Pharmaceutics, Friedrich-Schiller University of Jena, Ernst-Abbe-Platz 2, D-07743 Jena, Germany.

出版信息

Biosystems. 2005 Jul;81(1):49-63. doi: 10.1016/j.biosystems.2005.02.004. Epub 2005 Mar 19.

DOI:10.1016/j.biosystems.2005.02.004
PMID:15917128
Abstract

Calcium in ionic form is a second messenger connecting several input signals to several target processes in the cell. The question arises how one second messenger can transmit more than one signal simultaneously (bow-tie structure of signalling). Experimental data on calcium dynamics often show patterns of successive low-peak and high-peak oscillatory phases, known as bursting. Here, we propose that bursting calcium oscillations can perform the function of simultaneous transmission of two signals at physiological calcium concentrations, for example, by selective activation of two calcium-binding proteins. This differential regulation by periodic bursting is investigated in a theoretical model. The two proteins are assumed to be activated by calcium, and one of them is assumed to be subject to biphasic regulation due to additional inhibitory binding sites. To explore which characteristics of the complex signal could be responsible for independent regulation of low-peak activated and spike activated targets, different bursting patterns of simplified square pulses are applied. Depending on the change in the bursting pattern, one protein can be gradually activated at a constant level of the other protein's activity, or the two proteins can be activated simultaneously, or one protein can be activated while the other one is deactivated simultaneously. Thus, the two proteins can be regulated virtually independently.

摘要

离子形式的钙是一种第二信使,它将多种输入信号与细胞内的多个靶标过程联系起来。问题在于,一个第二信使如何能够同时传递不止一个信号(信号传导的蝴蝶结结构)。关于钙动力学的实验数据常常显示出连续的低峰和高峰振荡阶段的模式,即所谓的爆发。在此,我们提出,在生理钙浓度下,爆发性钙振荡可以通过例如选择性激活两种钙结合蛋白来实现同时传递两个信号的功能。通过一个理论模型研究了周期性爆发的这种差异调节。假设这两种蛋白由钙激活,并且其中一种蛋白由于额外的抑制性结合位点而受到双相调节。为了探究复杂信号的哪些特征可能负责对低峰激活靶标和尖峰激活靶标进行独立调节,应用了简化方波脉冲的不同爆发模式。根据爆发模式的变化,一种蛋白可以在另一种蛋白活性恒定的水平上逐渐被激活,或者两种蛋白可以同时被激活,或者一种蛋白被激活而另一种蛋白同时被失活。因此,这两种蛋白实际上可以被独立调节。

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