A global analysis of cross-talk in a mammalian cellular signalling network
A global analysis of cross-talk in a mammalian cellular signalling network
复制标题
DOI：
10.1038/ncb1418
复制
发表时间：
2006-06-01
影响因子：
21.3
通讯作者：
Ranganathan, Rama
中科院分区：
文献类型：
--
作者：
Natarajan, Madhusudan;Lin, Keng-Mean;Ranganathan, Rama
细胞信息处理需要细胞内信号通路大型网络的协调活动。通路之间的串扰提供了对刺激组合的复杂非线性反应，但人们对任何特定细胞中这些相互作用的密度知之甚少。在这里，我们分析了细胞信号转导联盟 (AfCS) 在 RAW 264.7 巨噬细胞中进行的大规模通路相互作用调查。研究了 22 种受体特异性配体，无论是单独的还是所有成对组合，用于 Ca2+ 动员、cAMP 合成、许多信号蛋白的磷酸化和细胞因子的产生。大量的非加性相互作用是明显的，这与已知的通路之间的串扰机制一致，但也揭示了许多新的相互作用。对串扰的全局分析表明，许多外部刺激集中在相对较少的交互机制上，以提供上下文相关的信号传导。
Cellular information processing requires the coordinated activity of a large network of intracellular signalling pathways. Crosstalk between pathways provides for complex non-linear responses to combinations of stimuli, but little is known about the density of these interactions in any specific cell. Here, we have analysed a large-scale survey of pathway interactions carried out by the Alliance for Cellular Signalling (AfCS) in RAW 264.7 macrophages. Twenty-two receptor-specific ligands were studied, both alone and in all pairwise combinations, for Ca2+ mobilization, cAMP synthesis, phosphorylation of many signalling proteins and for cytokine production. A large number of non-additive interactions are evident that are consistent with known mechanisms of cross-talk between pathways, but many novel interactions are also revealed. A global analysis of cross-talk suggests that many external stimuli converge on a relatively small number of interaction mechanisms to provide for context-dependent signalling.