Improved Kinetic Model of Short Term EGFR Signaling Network

Short Term Signaling by the Epidemical Growth Factor Receptor (EGFR) plays important roles in the process of cell growth, differentiation and replication. The kinetic model was developed by Kholodenko et al. in 1999 and reconstructed by Atef Suleiman in 2006. The simulation results agreed to a certain extent with experimental analysis of the effect of Epidermal Growth Factor (EGF) on the activation of downstream proteins, but the model deviated from experimental results of EGFR signaling at EGF concentrations below saturating level. In this paper, we improve the model by considering the degradation of protein in EGFR signal pathways. To evaluate effectively the error between simulation results and experimental data, we present a new definition (namely as acceptance degree) and calculate a reasonable fitness value, so that the genetic algorithm is used to obtain optimized degradation rates. The comparative research between the simulation results and experimental analysis show that the improved model is better than the kinetic model developed by Kholodenko et al. and Atef Suleiman. Our work can provide valuable insight into the dynamics of the signal-response relationship between the activated EGFR and the activation of downstream proteins.