Simulated Replicate Protein Activity Profiles. The protein activity profiles after treatment with all ligands for 1000 simulated cells. The graphs show the time course response of a subset of proteins in the model including: (A) receptor tyrosine kinases, (B) select intermediate signaling proteins, and (C) select transcription factor proteins including c-Fos and c-Jun. For instance, EGFR shows an initial increase in activity followed by inactivation due to feedback inhibition, which is consistent with our knowledge of receptor internalization and ubiquitination. We have not included similar feedback for the other receptor in the current model. Similarly, IRS is a hub signaling protein with a number of potential inhibitors and some of these are represented in our model. The activation of the MAPKs (ERK1/2) and transcription factors (AKT, c-Fos, c-Jun) in our simulation highlights the putative signaling cascade responsible for activating immediate early genes, which is a key step in cell cycle progression into S phase.