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Báo cáo khoa học: A modelling approach to quantify dynamic crosstalk between the pheromone and the starvation pathway in baker’s yeast

Cells must be able to process multiple information in parallel and, more-over, 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. | iFEBS Journal A modelling approach to quantify dynamic crosstalk between the pheromone and the starvation pathway in baker s yeast Jorg Schaber1 Bente Kofahl2 Axel Kowald1 and Edda Klipp1 1 Max Planck Institute for Molecular Genetics Berlin Germany 2 Humboldt University Berlin TheoreticalBiophysics Germany Keywords crossactivation crossinhibition filamentous growth pathway mathematicalmodel mating Correspondence E. Klipp Max Planck Institute for Molecular Genetics Ihnestr 63-73 14195 Berlin Germany Fax 49 30 804093 22 Tel 49 30 804093 16 E-mail klipp@molgen.mpg.de 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. Received 7 April2006 revised 2 June 2006 accepted 6 June 2006 doi 10.1111 j.1742-4658.2006.05359.x 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