A global analysis of cross-talk in a mammalian cellular signalling network.
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.
Natarajan
Madhusudan
M
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA.
Lin
Keng-Mean
KM
Hsueh
Robert C
RC
Sternweis
Paul C
PC
Ranganathan
Rama
R
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
D016207:Cytokines; D008024:Ligands; D000242:Cyclic AMP