Shutting the MAP Off - and On Again?

Abstract

Signal transduction pathways are the cellular information routes with which cells monitor their surrounding as well as their own state and adjust to environmental changes or hormonal stimuli. MAP kinase pathways are one type of signalling systems in eukaryotes that control stress responses, cell growth and proliferation as well as differentiation. In this study we compare two very well studied yeast signalling systems, the pheromone response pathway and the osmosensing HOG pathway. We have recently generated mathematical models that allow in silico analysis of signalling properties for both pathways. Deactivation of signalling is as important as activation because inappropriate pathway activation causes cell cycle arrest (in the cases studied here) or uncontrolled proliferation. Both pathways are transiently activated by their stimulus, i.e. mating pheromone and osmostress, respectively, indicating rigorous feedback mechanisms. However, the HOG pathway can readily be reactivated by a subsequent stimulus and this is important for its biological role in mediating osmoadaptation. The pheromone response pathway, however, is desensitised and is unable to respond for a certain period of time. While some mechanisms of feedback control are similar in both systems (such as the downregulatory role of protein phosphatases) the main difference seems to lie in the control of the sensors / receptors. The pheromone receptors are internalised and degraded following stimulation and hence are not available for further stimulation. The osmosensors on the other hand, seem to toggle between activated and deactivated state only controlled by osmotic changes. Together with subtle control by protein phosphatases this results in a system that is constantly receptive for stimulation. Keywords: hormonal stimuli, eukaryotes, protein phosphatases, osmosensors