A Mathematical Modeling of Signal Transduction Cascade on Raf-Akt Cross-Talk

MAPK signaling cascade initiated by the activation of EGF receptor (EGFR) has been experimentallywell studied and analyzed by mathematical modeling extensively [1, 3, 5]. Recently, several studiesshowed that some of growth hormone-stimulated membrane tyrosine kinase receptors interact withShc adaptor protein and phosphatidylinositol 3’-kinase (PI3K), and consequently PI3K-activated Aktinhibits Raf-1 and the following ERK activity which locates at the downstream of Shc signaling [2, 4].ThisinhibitionofRaf-1activitybyAktiscalledRaf-Aktcross-talk. SincethesetwoShc-RafandPI3K-Akt pathways exert opposite e ects on cell proliferation and di erentiation, a regulation balance ofthese two pathways is critical to de ne the cell fate. Based on the experimental proof reported to date,we developed a computational simulation model for a signal transduction cascade possessing Raf-Aktcross-talk to understand the regulation mechanism by analyzing the dynamics of kinase activities.