A Mathematical Modeling of Signal Transduction Cascade on Raf-Akt Cross-Talk
نویسندگان
چکیده
MAPK signaling cascade initiated by the activation of EGF receptor (EGFR) has been experimentally well studied and analyzed by mathematical modeling extensively [1, 3, 5]. Recently, several studies showed that some of growth hormone-stimulated membrane tyrosine kinase receptors interact with Shc adaptor protein and phosphatidylinositol 3’-kinase (PI3K), and consequently PI3K-activated Akt inhibits Raf-1 and the following ERK activity which locates at the downstream of Shc signaling [2, 4]. This inhibition of Raf-1 activity by Akt is called Raf-Akt cross-talk. Since these two Shc-Raf and PI3KAkt pathways exert opposite effects on cell proliferation and differentiation, a regulation balance of these two pathways is critical to define the cell fate. Based on the experimental proof reported to date, we developed a computational simulation model for a signal transduction cascade possessing Raf-Akt cross-talk to understand the regulation mechanism by analyzing the dynamics of kinase activities.
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