Article abstract
Nature Cell Biology 8, 571 - 580 (2006)
Published online: 14 May 2006 | doi:10.1038/ncb1418
A global analysis of cross-talk in a mammalian cellular signalling network
Madhusudan Natarajan1,2, Keng-Mean Lin1,2, Robert C. Hsueh1,2, Paul C. Sternweis1,2 & Rama Ranganathan1,3
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.
- Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390–-9050, USA.
- The Alliance for Cellular Signalling, University of Texas Southwestern Medical Center, Dallas TX 75390, USA.
- Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390–9050, USA.
Correspondence to: Rama Ranganathan1,3 e-mail: rama.ranganathan@utsouthwestern.edu
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