Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, London, UK.
Biophys J. 2013 Oct 1;105(7):1720-31. doi: 10.1016/j.bpj.2013.06.050.
Covalent modification cycles are basic units and building blocks of posttranslational modification and cellular signal transduction. We systematically explore different spatial aspects of signal transduction in covalent modification cycles by starting with a basic temporal cycle as a reference and focusing on steady-state signal transduction. We consider, in turn, the effect of diffusion on spatial signal transduction, spatial analogs of ultrasensitive behavior, and the interplay between enzyme localization and substrate diffusion. Our analysis reveals the need to explicitly account for kinetics and diffusional transport (and localization) of enzymes, substrates, and complexes. It demonstrates a complex and subtle interplay between spatial heterogeneity, diffusion, and localization. Overall, examining the spatial dimension of covalent modification reveals that 1), there are important differences between spatial and temporal signal transduction even in this cycle; and 2), spatial aspects may play a substantial role in affecting and distorting information transfer in modules/networks that are usually studied in purely temporal terms. This has important implications for the systematic understanding of signaling in covalent modification cycles, pathways, and networks in multiple cellular contexts.
共价修饰循环是翻译后修饰和细胞信号转导的基本单位和构建块。我们从基本的时间循环作为参考，系统地探索共价修饰循环中信号转导的不同空间方面，并专注于稳态信号转导。我们依次考虑扩散对空间信号转导的影响、超敏行为的空间类似物以及酶定位和底物扩散之间的相互作用。我们的分析表明需要明确考虑酶、底物和复合物的动力学和扩散传输（和定位）。它展示了空间异质性、扩散和定位之间复杂而微妙的相互作用。总的来说，检查共价修饰的空间维度表明，1），即使在这个循环中，空间和时间信号转导之间也存在重要差异；2），空间方面可能在以纯时间术语研究的模块/网络中影响和扭曲信息传递方面发挥重要作用。这对系统理解多种细胞环境中的信号转导在共价修饰循环、途径和网络中的作用具有重要意义。
