Note The mathematical model described here has been submitted to the Online Cellular Systems Modelling Database and can be accessed free of charge at http://jjj.biochem.sun.ac.za/database/schaber/index.html.
A modelling approach to quantify dynamic crosstalk between the pheromone and the starvation pathway in baker's yeast
Article first published online: 17 JUL 2006
Volume 273, Issue 15, pages 3520–3533, August 2006
How to Cite
Schaber, J., Kofahl, B., Kowald, A. and Klipp, E. (2006), A modelling approach to quantify dynamic crosstalk between the pheromone and the starvation pathway in baker's yeast. FEBS Journal, 273: 3520–3533. doi: 10.1111/j.1742-4658.2006.05359.x
- Issue published online: 17 JUL 2006
- Article first published online: 17 JUL 2006
- (Received 7 April 2006, revised 2 June 2006, accepted 6 June 2006)
- filamentous growth pathway;
- mathematical model;
Cells must be able to process multiple information in parallel and, moreover, they must also be able to combine this information in order to trigger the appropriate response. This is achieved by wiring signalling pathways such that they can interact with each other, a phenomenon often called crosstalk. In this study, we employ mathematical modelling techniques to analyse dynamic mechanisms and measures of crosstalk. We present a dynamic mathematical model that compiles current knowledge about the wiring of the pheromone pathway and the filamentous growth pathway in yeast. We consider the main dynamic features and the interconnections between the two pathways in order to study dynamic crosstalk between these two pathways in haploid cells. We introduce two new measures of dynamic crosstalk, the intrinsic specificity and the extrinsic specificity. These two measures incorporate the combined signal of several stimuli being present simultaneously and seem to be more stable than previous measures. When both pathways are responsive and stimulated, the model predicts that (a) the filamentous growth pathway amplifies the response of the pheromone pathway, and (b) the pheromone pathway inhibits the response of filamentous growth pathway in terms of mitogen activated protein kinase activity and transcriptional activity, respectively. Among several mechanisms we identified leakage of activated Ste11 as the most influential source of crosstalk. Moreover, we propose new experiments and predict their outcomes in order to test hypotheses about the mechanisms of crosstalk between the two pathways. Studying signals that are transmitted in parallel gives us new insights about how pathways and signals interact in a dynamical way, e.g., whether they amplify, inhibit, delay or accelerate each other.