Figure 6

Conversion of Analog Inputs Into Bimodal Responses by a Negative Feedback System Combined with Protein Expression Noise. An analog EGF stimulus (blue, green, and red correspond respectively to small, medium, and large stimulation magnitudes) induces variable but dose-dependent RasGTP responses in the cell population due to expression variability in the EGF pathway proteins. RasGTP responses are converted into ppERK responses in single cells according to a threshold-linear response governed by negative feedback (NF model). However, variability in RasGTP levels coupled with variability in ERK activation thresholds creates bimodal active ERK distributions at the population level despite the analog input and linear dose response at the single cell level.