A global analysis of cross-talk in a mammalian cellular signalling network

Madhusudan Natarajan, Keng Mean Lin, Robert C. Hsueh, Paul C. Sternweis, Rama Ranganathan

Research output: Contribution to journalArticlepeer-review

198 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)571-580
Number of pages10
JournalNature cell biology
Issue number6
StatePublished - Jun 2006

ASJC Scopus subject areas

  • Cell Biology


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