Journal of Proteome Research · 2008 · 45 citations · 41 references
Life SciencesBioinformaticsMolecular BiologyCell SignalingProtein-protein InteractionsSignal TransductionCell Signaling NetworksMolecular Interaction NetworksProtein-protein Interaction AnalysisProtein-protein Interaction NetworksRas Family OncogenesSignaling NetworksColocalization AnalysisGene Ontology EnrichmentPi3k SignalingPi3k-akt Signaling PathwayProtein-protein Interaction Network AnalysisRas SignalingRas Signaling PathwayRas-mitogen-activated Protein Kinase Signaling
The Ras-MAPK and PI3K-AKT pathways are conserved in metazoan organisms, which involve a series of signaling cascades and form the basis for numerous physiological and pathological processes. Here we report on yeast two hybrid screening results of a protein interaction network around the known components of human Ras-MAPK/PI3K pathways. A total of 42 independent cDNA library screenings resulted in 200 protein-protein interaction (PPI) pairs among 180 molecules. Most of the proteins formed a large cluster that contains 193 PPIs between 169 proteins. Seventy-four interactions indicate high-confidence according to bioinformatics analysis. The prey list contains high enrichment genes with specific Gene Ontology (GO) terms such as response to stress and response to external stimulus. Most interactions link the Ras signaling pathway with various cellular processes. Five interactions were validated by coimmunoprecipitation and colocalization assays in mammalian cells to confirm their in vivo interactions. This protein interaction network provides further insights into the molecular mechanism of Ras-MAPK/PI3K signaling pathways.
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