Figure 4. The Ras/Erk Module Is a High-Bandwidth, Low-Pass Filter, Faithfully Transmitting Dynamic Signals from 4 min to 2 hr.

(A) By applying oscillating light inputs and measuring responses, a pathway’s gain (output versus input amplitude) and phase shift (delay in peak response) can be obtained at each frequency. Possible frequency-response behaviors range from the narrow response of a band-pass filter to broad all-pass transmission.

(B) Left panel: Measuring the response to a light input containing multiple frequencies can efficiently reconstruct entire frequency responses from individual cells. Right panel: The frequency responses of five cells (blue curves) match a linear second-order low-pass filter (gray line). Upper timeline shows activation pulse timescales that correspond to stimulus frequencies shown on the x axis; typical Erk-response lifetimes (for PDGF and EGF stimulation) are shown.

(C) The mean cross-correlation between light input and nuclear Erk fold-change from five cells (gray line) and the predicted low-pass filter response of the linear frequency response model from (B) (blue line) show a 3 min delay of Erk activation following light input.

(D) Single-cell pulse responses from 25 cells (gray lines), shown with predictions of the linear frequency response model from (B) (blue lines).

(E) A model of signal transmission by the Ras/Erk module. Very short input stimuli are filtered and ignored by the Ras/Erk module, whereas inputs from minutes to hours are faithfully and efficiently transmitted by the MAPK cascade. The distinct patterns of Erk activity are then likely decoded by downstream dynamic filtering modules (black boxes).

See also Figure S3.