Coordination of crosstalk between MAPK-PKC pathways: An exploratory study

Networks of signaling pathways provide a robust mechanism for cells to respond to various biological stimuli. Cell adaptation through the viewpoint of an organising principle between two interconnected pathways - mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) is demonstrated. A multilevel system representation of the pathways is used to determine the pathway components contributing to the adaptive behaviour and coordination. The adaptation can be thought of as being manifested by a change in parameters of the coordinator. In silico experiments are conducted using MAPK-PKC mathematical model in the literature, which is modularised using biological functionality. Through extensive, guided parametric in silico experiments, the PLA₂ subsystem is shown to be a coordinator. Results show that varying parameters of the coordinator not only activate the network of pathways where otherwise the pathway activity is very low, but also reveal the ability of the system to activate itself in the absence of the input, indicating relevance of the principle of bounded autonomy.