Author: ["Madhusudan Natarajan","Keng-Mean Lin","Robert C. Hsueh","Paul C. Sternweis","Rama Ranganathan"]
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Abstract
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.Cite this article
Natarajan, M., Lin, KM., Hsueh, R. et al. A global analysis of cross-talk in a mammalian cellular signalling network. Nat Cell Biol 8, 571–580 (2006). https://doi.org/10.1038/ncb1418 