Mathematical Investigation of How Oncogenic Ras Mutants Promote Ras Signaling

We have used a mathematical model of the Ras signaling network to link observable biochemical properties with cellular levels of RasGTP. Although there is abundant data characterizing Ras biochemistry, attributing specific changes in biochemical properties to observed phenotypes has been hindered by the scope and complexity of Ras regulation. A mathematical model of the Ras signaling module, therefore, appeared to be of value for this problem. The model described the core architecture shared by pathways that signal through Ras. Mass-action kinetics and ordinary differential equations were used to describe network reactions. Needed parameters were largely available in the published literature and resulted in a model with good agreement to experimental data. Computational analysis of the model resulted in several unanticipated predictions and suggested experiments that subsequently validated some of these predictions.