title: A global analysis of cross-talk in a mammalian cellular signalling network.
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.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA.
authors.forename: Madhusudan
authors.initials: M
authors.lastname: Natarajan
authors.forename: Keng-Mean
authors.initials: KM
authors.lastname: Lin
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hsueh
authors.forename: Paul C
authors.initials: PC
authors.lastname: Sternweis
authors.forename: Rama
authors.initials: R
authors.lastname: Ranganathan
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D016000:Cluster Analysis; D000242:Cyclic AMP / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D008024:Ligands; D008264:Macrophages; D051379:Mice; D010766:Phosphorylation; D020239:Receptor Cross-Talk; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D008024:Ligands; D000242:Cyclic AMP