Simulation and sensitivity analysis of phosphorylation of EGFR signal transduction pathway in PC12 cell model.

Abstract

The epidermal growth factor receptor (EGFR) signalling pathway is a complex signalling process with a wide network of interactions. The activation of the mitogen-activated protein kinases (MAPKs) cascade by this activated EGFR has been well studied. MAPKs form a highly integrated network, which is essential for certain specialised cell functions. This paper presents a kinetic model for the MAPK pathway downstream of the EGFR using a biochemical simulator. The model includes 30 signalling events and 29 signalling molecules. The time course data were examined for the activation of each signalling component. The simulation provides a large volume of data, by monitoring the kinetics of the signalling components, which were compared experimentally using the PC12 cell line. The kinetic model corresponded well with the experimental results observed in the EGFR induced activation of proteins. An examination of the kinetic analysis of the multiple signalling events provides a quantitative framework for representing the EGFR signalling network.