Defining a modular signalling network from the fly interactome

Background: Signalling pathways relay information by transmitting signals from cell surface receptors to intracellular effectors that eventually activate the transcription of target genes. Since signalling pathways involve several types of molecular interactions including protein-protein interactions, we postulated that investigating their organization in the context of the global protein-protein interaction network could provide a new integrated view of signalling mechanisms. Results: Using a graph-theory based method to analyse the fly protein-protein interaction network, we found that each signalling pathway is organized in two to three different signalling modules. These modules contain canonical proteins of the signalling pathways, known regulators as well as other proteins thereby predicted to participate to the signalling mechanisms. Connections between the signalling modules are prominent as compared to the other network's modules and interactions within and between signalling modules are among the more central routes of the interaction network. Conclusion: Altogether, these modules form an interactome sub-network devoted to signalling with particular topological properties: modularity, density and centrality. This finding reflects the integration of the signalling system into cell functioning and its important role connecting and coordinating different biological processes at the level of the interactome.