Attisano Liliana, Wrana Jeffrey L
Department of Biochemistry and Donnelly CCBR, University of Toronto 160 College Street, Toronto, ON Canada, M5S 3E1.
F1000Prime Rep. 2013 Jun 3;5:17. doi: 10.12703/P5-17. Print 2013.
Complete sequences of animal genomes have revealed a remarkably small and conserved toolbox of signalling pathways, such as TGF-β and WNT that account for all biological diversity. This raises the question as to how such a limited set of cues elaborates so many diverse cell fates and behaviours. It is now clear that components of signalling pathways are physically assembled into higher order networks that ultimately dictate the biological output of pathway activity. Intertwining of pathways is thus emerging as a key feature of a large, integrated and coordinated signalling network that allows cells to read a limited set of extrinsic cues, but mount the diverse responses that underpin successful development and homeostasis. Moreover, this design principle confounds the development of effective therapeutic interventions in complex diseases, such as cancer.
动物基因组的完整序列揭示了一组非常小且保守的信号通路工具箱，如转化生长因子-β（TGF-β）和WNT信号通路，它们构成了所有的生物多样性。这就引发了一个问题：如此有限的一组信号是如何产生如此多不同的细胞命运和行为的。现在很清楚的是，信号通路的组成部分在物理上组装成更高层次的网络，最终决定了通路活性的生物学输出。因此，通路的交织正成为一个大型、整合且协调的信号网络的关键特征，该网络使细胞能够解读有限的一组外在信号，但做出各种反应，这些反应是成功发育和维持体内平衡的基础。此外，这种设计原则也给复杂疾病（如癌症）的有效治疗干预措施的开发带来了困难。
