Optimal ratio of scaffold complex to free Fus3 to maximise the accumulation of phosphorylated Fus3 in yeast pheromone signalling pathway

In this study, the author considers the design rule of the intracellular signalling pathway. In yeast pheromone signalling pathway, scaffold Ste5 tethers the components of signalling pathway, Ste11, Ste7 and Fus3. Even though scaffold complex is independently produced before stimuli, excessively expressed Fus3 as compared with scaffold exists in cytoplasm as free kinase. How the ratio of scaffold complex to the free Fus3 is determined is not clear yet. First, the contribution of free Fus3 to signal transduction is theoretically shown by using a simplified model of pheromone signalling pathway. Next, the optimum expression levels of Ste5, Ste11, Ste7 and Fus3 are systematically explored by using the detailed model and genetic algorithm under the constraint that the total expression level of these four genes is limited. Excessive expression of Fus3 is advantageous for the efficient signalling without stall of the signal transduction. The result suggests that the component of signalling pathway is optimally expressed to maximise the accumulation of phosphorylated Fus3 at a fixed time point under the constraint that the total gene expression is limited. The proposed model provides further insight into the signalling network from the point of view of not only its function but also its optimality.