Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College London, UK.
Phys Biol. 2012 Aug;9(4):045009. doi: 10.1088/1478-3975/9/4/045009. Epub 2012 Aug 7.
Covalent modification cycles are a ubiquitous feature of cellular signalling networks. In these systems, the interaction of an active enzyme with the unmodified form of its substrate is essential for signalling to occur. However, this interaction is not necessarily the only enzyme-substrate interaction possible. In this paper, we analyse the behaviour of a basic model of signalling in which additional, non-essential enzyme-substrate interactions are possible. These interactions include those between the inactive form of an enzyme and its substrate, and between the active form of an enzyme and its product. We find that these additional interactions can result in increased sensitivity and biphasic responses, respectively. The dynamics of the responses are also significantly altered by the presence of additional interactions. Finally, we evaluate the consequences of these interactions in two variations of our basic model, involving double modification of substrate and scaffold-mediated signalling, respectively. We conclude that the molecular details of protein-protein interactions are important in determining the signalling properties of enzymatic signalling pathways.
共价修饰循环是细胞信号网络的普遍特征。在这些系统中，活性酶与未修饰形式的底物相互作用对于信号转导的发生至关重要。然而，这种相互作用不一定是唯一可能的酶-底物相互作用。在本文中，我们分析了一种基本的信号模型的行为，其中可能存在额外的非必需的酶-底物相互作用。这些相互作用包括酶的无活性形式与其底物之间的相互作用，以及酶的活性形式与其产物之间的相互作用。我们发现这些额外的相互作用可以分别导致增加的敏感性和双相反应。额外相互作用的存在还显著改变了反应的动力学。最后，我们在我们的基本模型的两个变体中评估了这些相互作用的后果，分别涉及底物的双重修饰和支架介导的信号转导。我们的结论是，蛋白质-蛋白质相互作用的分子细节对于确定酶促信号通路的信号转导特性很重要。
