Skip to main content
. 2018 Jun 19;14(6):e1006192. doi: 10.1371/journal.pcbi.1006192

Fig 3. Analysis of time-dependent signalling pathway activation in response to dual inhibition of EGFR/PYK2.

Fig 3

(a-b) Simulations of time-dependent phosphorylation of STAT3 and ERK in response to Gefitinib (Gef) and PF396 (PF) alone, or in combination. (c) Effects of Gefitinib and PF396 treatment on the protein levels and activation states of indicated signalling proteins upon indicated time-points of EGF stimulation. Shown are representative western blotting (WB) results. (d-e) Simulation data of steady-state pERK and pSTAT3 levels in response to single-drug and combined treatment of Gefitinib and PF396 for 24h. (f-g) Experimental data of steady-state pERK and pSTAT3 levels in response to single-drug and combined treatment of Gefitinib and PF396 for 24h. (h-k) Sensitivity analysis of the feedback regulation. Simulations of the effect of time-dependent feedback perturbation on pERK and pSTAT3 levels. F1-F4 indicates the feedback-related links perturbed for analysis (for detail see S4 Table). Each feedback-related link was alternatively perturbed by inhibiting its strength by 20%. (l-o) Steady-state levels of pERK and STAT3 following 48h of drug treatments comparing control and perturbations of the feedback loops.