Dynamic Analysis of Feedback Loops in Extra-Cellular Signal Regulated Kinase Signal Network

Extra-cellular signal regulated kinase (ERK) signal network plays an important role in regulating the fundamental cellular functions such as cell proliferation, survival, differentiation and motility. Development and analysis of mathematical model can help us acquire a deep understanding of the complex behavior of ERK signal transduction network. This paper presents a computational model that offers an integrated quantitative and dynamic simulation of ERK signal transduction network, activated by epidermal growth factor (EGF). The mathematic model contains the activation kinetics of the pathway, a multitude of feedback loops and connection of scaffold proteins. The model provides insight into signal-response relationships between the binding of EGF to its receptor at the cell surface and activation of downstream proteins in the signaling cascade. The different influence of positive and negative feedback loops of the ERK signal transduction pathway were mainly analyzed, indicating that feedback loops were the main impacting factor to the oscillation of ERK signal transduction pathway. The predictions of this oscillation of ERK activation agree well with the literature. It can lead to signal waves of the downstream substrates and induce corresponding biological behaviors.