Departments of Medicine and Bioengineering, University of California at San Diego, La Jolla, California, USA.
Nat Methods. 2010 Oct;7(10):801-5. doi: 10.1038/nmeth.1506.
Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps.
丝裂原活化蛋白激酶 (MAPK) 途径构成了哺乳动物细胞信号转导的核心。在这里，我们采用系统的实验和计算方法来绘制 2269 个人类 MAPK 相关蛋白与其他细胞机制之间的相互作用，并将这些数据组装成功能模块。包括与酵母的保守性在内的多种证据支持了一个由 641 个相互作用组成的核心网络。使用小干扰 RNA 敲低，我们观察到大约三分之一的 MAPK 相互作用蛋白调节了 MAPK 介导的信号转导。我们发现 Na-H 交换器 NHE1 是一个潜在的 MAPK 支架，发现 HSP90 伴侣蛋白与 MAPK 途径之间存在联系，并鉴定出 MUC12 是人类信号粘蛋白 Msb2 的类似物。这项研究提供了大量的 MAPK 相互作用和克隆文库，它说明了一种基于实验衍生的蛋白质相互作用图谱的功能细化来探测信号网络的方法。
