Theoretical Analysis of the Epidermal Growth Factor Receptor Signaling Network under the Control Condition and After Chronic Ethanol Treatment
Markevich N.I., Moehren G., Hoek J.
Institute of Theoretical and Experimental Biophysics RAS, Pushchino, 142290, Russia
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Abstract. Mathematical model consisting of 186 ordinary differential equations was employed to account for our experimental data on autophosphorylation of EGF receptor under control condition and after chronic ethanol treatment. Computer fitting procedure was used to fit the computational model results to experimental data using different hypotheses about sites sensitive to ethanol. It was shown that the model accounts for experimental data quantitatively at the suggestion that chronic ethanol treatment induces a decrease in an active fraction of EGFR in the plasmatic membrane as well as the rate of dimerization of EGFR. Besides, additional hypothesis was used that ethanol decreases EGFR phosphatases activities due to a decrease in the protein level and catalytic constants.
Key words: epidermal growth factor (EGF), signaling, ethanol, mathematical model.