Figure 1. Overview of known mechanisms of MAPK signaling plasticity.

Many reported interactions may not occur in the context of own experiments. Here, we review two types of mechanisms that yield differences between reported and experimental interactions. First, interactions can dynamically arise during observation to adapt to perturbation - here termed dynamic signaling rearrangements. Second, unreported interactions can be present from the unperturbed, onset of observation - here termed context-dependent topology. The upper row shows two known dynamic MAPK signaling rearrangements, which are achieved by preferentially expressing alternate transcripts to maintain tumor proliferation upon of treatment. In the middle section, three mechanisms are shown to change network topology in order to grant cells the ability to trigger a specific response to a ligand. Such specificity is achieved by tightly regulating known crosstalk interactions, thereby, preventing cross-signaling between pathways. Below, 3 rows describe different robustness mechanisms. When such mechanisms are present, an increase in the total protein concentration of a certain signaling regulator due to expression noise can be compensated to maintain the functionality of the pathway. The spectrum of mechanisms leading to both dynamic rearrangements and context-dependent topologies illustrates the need for methods to corroborate the activity of reported interactions in a timely and cell type specific manner.