Natarajan Madhusudan, Lin Keng-Mean, Hsueh Robert C, Sternweis Paul C, Ranganathan Rama
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA.
Nat Cell Biol. 2006 Jun;8(6):571-80. doi: 10.1038/ncb1418. Epub 2006 May 14.
Cellular information processing requires the coordinated activity of a large network of intracellular signalling pathways. Cross-talk 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.
细胞信息处理需要细胞内信号通路的大型网络协同活动。通路之间的相互作用使得细胞对多种刺激组合产生复杂的非线性反应，但对于任何特定细胞中这些相互作用的密度了解甚少。在此，我们分析了细胞信号联盟（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，分别单独以及以所有两两组合的形式，检测其对钙离子动员、环磷酸腺苷（cAMP）合成、多种信号蛋白的磷酸化以及细胞因子产生的影响。大量非加性相互作用明显存在，这与已知的通路间相互作用机制一致，但同时也揭示了许多新的相互作用。对相互作用的全局分析表明，许多外部刺激汇聚于相对较少的相互作用机制，以实现依赖于背景的信号传导。
