An information thermodynamic approach quantifying MAPK-related signaling cascades by average entropy production rate

ABSTRACTInformation thermodynamics has recently greatly developed the application for analysis of biological phenomenon. During the signal transduction, entropy production from phosphorylation of signal molecule is produced at individual step production. Using this value, average entropy production rate (AEPR) is computable.In the current study, AEPR in each signal step was analyzed using experimental data from previously reported studies of the mitogen-activated protein kinases (MAPK) cascade. The result revealed that the differences of AEPR is smaller when using ligands, suggesting that AEPR is one of the attributes of the given cascade and useful for quantitative analysis. This consistency of AEPR suggests that the number of signal events is maximized, in other words, signaling efficiency is maximized. In conclusion, the current information theoretical approach provides not only a quantitative means for comparison of responses to a specified extracellular stimulation, but also a method for evaluation of active cascades.SynopsisA variety of methods for quantifying intracellular signal transduction have been proposed. Herein, a novel method of quantification by integrated analysis consisting of kinetics, non-equilibrium thermodynamics, fluctuation theorem and graph theory was attempted.Signal transduction can be computed by entropy production amount from the fluctuation in the phosphorylation reaction of signaling molecules.By Bayesian analysis of the entropy production rates of individual steps, they are consistent through the signal cascade.