Figure 5

Model calibration simulations. The mathematical model for early signaling events reproduces the early dynamics for activation of selected pathways downstream from ErbB1. Simulated results (lines) are compared against the experimental observations (symbols) used to calibrate the mathematical model. The uncertainty in the model predictions obtained from each are represented by three lines of the same color: the most likely prediction is represented by the solid lines and the dashed lines represent the 95th and 5th percentile of the predicted response. The results for each of the three parallel chains are shown in different colors: Chain 1 (Blue), Chain 2 (Black), and Chain 3 (Red). (A) Simulated response (lines) versus measured total ErbB1 expression in 184A1 cells (▽[20]). (B) Comparison to the phosphorylated form of ErbB1 was reported as a percentage of the total ErbB1 expression (○ [18], □ [30], and △ [31]). (C) The simulated fraction of total cellular Grb2 bound to activated ErbB1 (line) is compared against experimental values (○ [18]). (D) Simulated (line) and measured (circles) [18]) percentage of total Grb2 bound to activated Shc. (E) Simulated (line) and measured (□ [30]) percentage of total Sos bound to activated ErbB1. (F) The phosphorylated form of Shc, reported as a percentage of total Shc (○ [18], △[31], ◇ [22]), is compared against the simulated value (line). (G) Comparison of simulated (line) versus the phosphorylated form of PLCγ-1, reported as a percentage of total PLCγ-1 (△ [31]). (H) The active form of Ras (RasGTP), reported as a percentage of total Ras (□ [30]), is compared against the simulated values (line). The initial conditions used in the simulation are tabulated (see Additional file 1: Table S3). With the exception of p-Shc observed by [22], all observations were made following exposure to 20 nM EGF in primary rat hepatocytes. In panel F, the measurements by [22] were obtained following exposure to 10 nM EGF in MCF-7 cells.