Cells can respond to various stimulations by changing the localization of signaling proteins. One can imagine this as a computation, in which the dynamics of the signaling molecules in the cell represent the input signals. Using live-imaging of individual living cells, we follow the dynamic nuclear accumulation of the ERK2 protein of the MAPK signal transduction pathway upon stimulation with epidermal growth factor (EGF). We show that part of this computation of the response has a feature named fold-change response. The flow of information is further processed by yet unknown cellular mechanisms in a fold-change manner, suggesting that the ERK2 system compensates for natural biological noise despite large variation in nuclear basal levels.
Theoretical studies indicate that the fold-change response can be explained by one of the most common network motifs in topological networks, the incoherent feed-forward loop (I1-FFL). The fold-response feature of the I1-FFL applies to the entire shape of the response, including its amplitude and duration. Fold-response can help buffer cell-to-cell variation in the level of regulatory proteins, and help overcome noise in the signal. This provides a view of this signaling pathway at the individual cell level and suggests that fold rather than absolute changes in nuclear level characterize the response of this pathway.
