Model-Aided Analysis of Cellular Signal Transduction Pathways

Mariko Hatakeyama, RIKEN Genomic Sciences Center

Deregulation of ErbB receptors is implicated in various kinds of human cancers. We mathematically modeled the ligand-induced ErbB signal transduction pathways based on the experimental data. Co-expression of the different ErbB receptors induced dramatic changes in biochemical dynamics as well as in protein-protein interaction (PPI) patterns. To understand regulatory mechanisms of signal transduction pathways at the molecular level, we applied molecular dynamics (MD) simulation. Binding affinities of the PPI or its novel binding patterns between ErbB receptors and Grb2, PI3K, and Shc can be predicted by MD simulation. Currently we are working to identify gene regulatory networks induced by ErbB signaling pathways.