Schematic and simulations of original Brown et al. (2004) EGF model: (A) This is a basic schematic of the original model of the EGF activated ERK pathway developed by ; activating reactions are shown with solid lines ending in arrows whereas deactivating reactions are shown with dashed lines ending in diamonds. We used this model to investigate the effects of a Ras mutation (highlighted in red) and an EGFR mutation (green), as well as the roles of the SOS (highlighted with red line) and Raf-1 (green) negative feedback loops. All the lines in graph (B) and (C) represent simulated active ERK levels over 60 minutes. (B) The blue line represents active ERK levels from the normal EGF model, whereas the green and red lines represent active ERK levels from the Ras and EGFR mutation models, respectively; the EGFR mutation (green line) is practically indistinguishable from the normal simulation (blue line) and hence the blue line is obscured from view. (C) The blue line is the same as in (B), whereas the green line represents active ERK levels after the Raf-1 feedback loop has been knocked out, and the red line represents active ERK levels after the Akt feed-forward and SOS feedback loops have been knocked out.