Flux Optimization in Human Specific Map-Kinase Pathways: A Systems Biology Approach to Study Cancer

Mitogen-Activated Protein Kinase (MAP kinases) transduces signals that are involved in a multitude of cellular pathways and functions in response to variety of ligands and cell stimuli. Aberrant or inappropriate functions of MAPKs have now been identified in diseases ranging from Cancer to Alzheimer disease to Leshmaniasis however the pathway is still growing and little is known about the dynamics of the pathway. Here we model the MAPK metabolic pathways and thus find the key metabolites or reactions involved on perturbing which the transcription factors are affected. The approach, which we used for modeling of this pathway, is Flux Balance Analysis (FBA). Further we established the growth factors EGF, PDGF were also responsible for the determination of downstream species concentrations. Tuning the parameters gave the optimum kinetics of the growth factor for which the downstream events were at the minimum. Also the Ras and Braf steady state concentrations were significantly affected when the Growth factor kinetics were tuned. This type of study can shed light on controlling various diseases and also may be helpful for identifying important drug targets.