Schrum Adam G, Gil Diana
Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Clin Exp Pharmacol. 2012 Dec 21;2(3):S3.001. doi: 10.4172/2161-1459.S3-001.
The collective Protein:Protein Interactions (PPI) of a cell are thought to represent a system with emergent network properties that integrate signals from a multiplicity of inputs into coordinated responses. It is hypothesized that the PPI network supplies both specificity for many distinct signals that utilize common intermediate pathways, and also robustness by allowing specific signals to be communicated by alternate routes. Progress with genetic networks points to these concepts, but the extent to which PPI networks possess these properties has not been empirically tested, due to lack of quantitative data needed for such assessments. Here, a hypothetical physiologic PPI network is used to illustrate how signaling robustness and specificity could be manifest under conditions of (i) deletion mutation, or (ii) changes in signaling due to variation in environmental conditions or stimuli. It is proposed that advances in technology enabling empirical analysis of PPI network principles will have the potential to significantly impact basic understanding of signaling mechanisms, and contribute to the generation of novel applications in drug screening and pharmacology.
细胞中的蛋白质-蛋白质相互作用（PPI）总体被认为代表了一个具有涌现网络特性的系统，该系统将来自多种输入的信号整合为协调的反应。据推测，PPI网络既为许多利用共同中间途径的不同信号提供特异性，又通过允许特定信号通过替代途径进行传递而提供稳健性。遗传网络的研究进展指向了这些概念，但由于缺乏进行此类评估所需的定量数据，PPI网络在多大程度上具有这些特性尚未得到实证检验。在此，使用一个假设的生理PPI网络来说明在（i）缺失突变或（ii）由于环境条件或刺激变化导致的信号传导变化的情况下，信号稳健性和特异性是如何体现的。有人提出，能够对PPI网络原理进行实证分析的技术进步有可能显著影响对信号传导机制的基本理解，并有助于在药物筛选和药理学中产生新的应用。
