Stochastic response of ultrasensitivity: Optimized switching of mitogen activated protein kinase (MAPK) cascade

Abstract

The intricate dynamics of ultrasensitive transitions within mitogen-activated protein kinase (MAPK) cascade circuits regulate the diverse physiological activities in a living organism emphasizing their pivotal role in cellular signal transduction. We have shown that the generic features of ultrasensitive transition often characterized through critical slowing down, however, one can have a theoretical estimate of such catastrophic transition using a stochastic response function, called early warning signals (EWS). EWS is composed of slowing down of decay of correlation and divergence of fluctuation phenomenon under very low perturbation. It is shown that the ultrasensitive transition arises depending on the trade off between the cycle number and essential activation parameter. Therefore, the transition point is kinetically optimized by these two parameters so that a high activation energy is surmounted through multiple steps and here we have shown that EWS as stochastic response functions can capture this optimization most effectively.