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


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.

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  1. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390–-9050, USA.
  2. The Alliance for Cellular Signalling, University of Texas Southwestern Medical Center, Dallas TX 75390, USA.
  3. 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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