Figure 6. ERK activation is an ubiquitous master regulator of the integrated pc-Fos responses.

(A-C) PC-12 cells were stimulated with 10 nM EGF or 10 nM NGF for indicated periods of time and responses were measured with western blotting (proteins) or qRT-PCR (mRNA). Data were normalized by dividing them by the maximum value of the HRG-induced responses. (D-E) MCF-7 cells were stimulated with 10 nM EGF + 100 nM PMA. F. The ppERK input is characterized by three parameters: the peak amplitude A_p, the peak time T_p and the decay time τ. G. Quantitative relationship between the integrated pc-Fos output and the ppERK decay time τ. Data points correspond to experimental data for various ligand doses in MCF-7 and PC-12 cells, which are indicated by text boxes. The ppERK decay time τ was calculated from experimental data (see Supp. Methods, Core Model Description, ${\tau }_{\mathit{in}}^d$). For simulations, the values for A_p and T_p were fixed at 1 and 10 min., respectively, as is commonly observed for ppERK responses. Calculation of the integrated pc-Fos responses from experimental data is described in Supp. Methods. For all relevant panels, error bars denote standard error for at least three independent experiments, representative blot images can be found in Fig. S4, and solid lines denote simulations. For all panels, simulations were done using the core model. See also Fig. S4.