Limits to the rate of information transmission through the MAPK pathway

Two important signalling pathways of NF-kappa B and ERK transmitmerely 1 bit of information about the level of extracellular stimulation. It is thus unclear how such systems can coordinate complex cell responses to external cues. We analyse information transmission in the MAPK/ERK pathway that converts both constant and pulsatile EGF stimulation into pulses of ERK activity. Based on an experimentally verified computationalmodel, we demonstrate that, when input consists of sequences of EGF pulses, transmitted information increases nearly linearly with time. Thus, pulse-interval transcoding allows more information to be relayed than the amplitude-amplitude transcoding considered previously for the ERK and NF-kappa B pathways. Moreover, the information channel capacity C, or simply bitrate, is not limited by the bandwidth B = 1/tau, where tau approximate to 1 h is the relaxation time. Specifically, when the input is provided in the form of sequences of short binary EGF pulses separated by intervals that are multiples of tau/n (but not shorter than tau), then for n = 2, C approximate to 1.39 bit h(-1); and for n = 4, C approximate to 1.86 bit h(-1). The capability to respond to random sequences of EGF pulses enables cells to propagate spontaneous ERK activity waves across tissue.