Locasale Jason W
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
BMC Syst Biol. 2008 Dec 17;2:108. doi: 10.1186/1752-0509-2-108.
Signal duration (e.g. the time over which an active signaling intermediate persists) is a key regulator of biological decisions in myriad contexts such as cell growth, proliferation, and developmental lineage commitments. Accompanying differences in signal duration are numerous downstream biological processes that require multiple steps of biochemical regulation.
Here we present an analysis that investigates how simple biochemical motifs that involve multiple stages of regulation can be constructed to differentially process signals that persist at different time scales. We compute the dynamic, frequency dependent gain within these networks and resulting power spectra to better understand how biochemical networks can integrate signals at different time scales. We identify topological features of these networks that allow for different frequency dependent signal processing properties.
We show that multi-staged cascades are effective in integrating signals of long duration whereas multi-staged cascades that operate in the presence of negative feedback are effective in integrating signals of short duration. Our studies suggest principles for why signal duration in connection with multiple steps of downstream regulation is a ubiquitous motif in biochemical systems.
信号持续时间(例如活性信号中间体持续存在的时间)是细胞生长、增殖和发育谱系定向等众多情况下生物决策的关键调节因子。伴随信号持续时间的差异存在许多下游生物学过程,这些过程需要多个生化调节步骤。
在此,我们进行了一项分析,研究如何构建涉及多个调节阶段的简单生化基序,以对在不同时间尺度上持续存在的信号进行差异处理。我们计算这些网络内的动态、频率依赖性增益以及由此产生的功率谱,以更好地理解生化网络如何在不同时间尺度上整合信号。我们确定了这些网络的拓扑特征,这些特征允许不同的频率依赖性信号处理特性。
我们表明,多级联在整合长时间信号方面有效,而在负反馈存在下运行的多级联在整合短时间信号方面有效。我们的研究提出了一些原则,解释了为何与下游多个调节步骤相关的信号持续时间是生化系统中普遍存在的基序。