Kinase Inhibition Leads to Hormesis in a Dual Phosphorylation-Dephosphorylation Cycle
Fig 5
Dose response curves of type-1 (green line) and type-2 (blue line) cells in the presence of an inhibitor (inhtot), in the case when motif Eq (1) is bistable. A logistic curve (red line) is fitted to sample points (red dots) generated numerically from a population containing 88% type-1 cells and 12% type-2 cells. The logistic fit to data is used to estimate IC50 of the total population (see Supplementary Information). In the absence of the inhibitor type-1 cells are at CPP,1* stead state while type-2 cells are at CPP,2*. In the presence of the inhibitor at IC50, while the total population exhibits 50% inhibition, the same concentration has the opposing effects on the two sub-populations. In particular, type-1 cells are inhibited, which can be deduced from the observation that the steady state CPP,1** calculated at the population-level IC50 is lower than the steady state CPP,1* calculated in the absence of the inhibitor. Contrary to this type-2 cells are stimulated since the steady state CPP,2** calculated at the population-level IC50 is higher than the steady state CPP,2* calculated in the absence of the inhibitor. This stimulatory effect is amplified even further for IC*<IC50, as seen by comparing the relatively high values of the steady state CPP,2x at IC* to the relatively low values of the steady state CPP,2* in the absence of the inhibitor.