Research ResourceSystems Biology

A Directed Protein Interaction Network for Investigating Intracellular Signal Transduction

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Sci. Signal.  06 Sep 2011:
Vol. 4, Issue 189, pp. rs8
DOI: 10.1126/scisignal.2001699

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Finding More Pieces to the Signaling Puzzle

Even well-studied pathways are likely to be incomplete in terms of our knowledge of all the components and their relationships, and the larger interconnected network that represents the true cellular regulatory landscape remains woefully unknown. Vinayagam et al. used an automated yeast two-hybrid interaction mating assay to identify protein-protein interactions (PPIs) among human proteins and then integrated that PPI data set with previously published data to create an undirected human PPI network connecting 9832 proteins through 39,641 interactions. The authors then applied a Bayesian learning strategy to assign direction to the interactions among the proteins. The resulting directed network enabled them to evaluate growth factor–induced protein phosphorylation dynamics and to identify previously unknown modulators of the extracellular signal–regulated protein kinase pathway, of which 18 were validated with cell-based assays. This strategy should prove useful in completing the puzzle of the cellular regulatory network.