Abstract:
Very often dysfunctional aspects of various signalling networks are found to be associated with human diseases and disorders. The major characteristics of signal transduction pathways are specificity, amplification of the signal, desensitisation and integration, which is accomplished not solely, but majorly by proteins. Array-based profiling of protein-protein and other biomolecular interactions is a versatile approach, which holds immense potential for multiplex interactome mapping and provides an inclusive representation of the signal transduction pathways and networks. Protein microarrays such as analytical protein microarrays (antigen-antibody interactions, autoantibody screening), RP microarrays (interaction of a particular ligand with all the possible targets in cell), functional protein microarrays (protein-protein or protein-ligand interactions) are implemented for various applications, including analysis of protein interactions and their significance in signalling cascades. Additionally, successful amalgamation of the array-based approaches with different label-free detection techniques allows real-time analysis of interaction kinetics of multiple interaction events simultaneously. This review discusses the prospects, merits and limitations of different variants of array-based techniques and their promising applications for studying the modifications and interactions of biomolecules, and highlights the studies associated with signal transduction pathways and their impact on disease pathobiology.
摘要:
经常发现各种信号网络的功能失调方面与人类疾病和病症有关。信号转导通路的主要特征是特异性,信号的放大,脱敏和整合,这不仅仅是完成的,但主要是蛋白质。基于阵列的蛋白质-蛋白质和其他生物分子相互作用的分析是一种通用的方法,它具有多重相互作用组作图的巨大潜力,并提供了信号转导途径和网络的包容性表示。蛋白质微阵列,如分析蛋白质微阵列(抗原-抗体相互作用,自身抗体筛查),RP微阵列(特定配体与细胞中所有可能的靶标的相互作用),功能性蛋白质微阵列(蛋白质-蛋白质或蛋白质-配体相互作用)可用于各种应用,包括分析蛋白质相互作用及其在信号级联中的意义。此外,基于阵列的方法与不同的无标记检测技术的成功合并允许同时对多个相互作用事件的相互作用动力学进行实时分析。这篇综述讨论了前景,基于阵列的技术的不同变体的优点和局限性及其在研究生物分子的修饰和相互作用方面的有希望的应用,并重点介绍了与信号转导途径相关的研究及其对疾病病理生物学的影响。