Modelling the dynamics of the yeast pheromone pathway.
We present a mathematical model of the dynamics of the pheromone pathways in haploid yeast cells of mating type MATa after stimulation with pheromone alpha-factor. The model consists of a set of differential equations and describes the dynamics of signal transduction from the receptor via several steps, including a G protein and a scaffold MAP kinase cascade, up to changes in the gene expression after pheromone stimulation in terms of biochemical changes (complex formations, phosphorylations, etc.). The parameters entering the models have been taken from the literature or adapted to observed time courses or behaviour. Using this model we can follow the time course of the various complex formation processes and of the phosphorylation states of the proteins involved. Furthermore, we can explain the phenotype of more than a dozen well-characterized mutants and also the graded response of yeast cells to varying concentrations of the stimulating pheromone.
Kofahl
Bente
B
Humboldt University Berlin, Theoretical Biophysics, Invalidenstrasse 43, 10115 Berlin, Germany.
Klipp
Edda
E
D018797:Cell Cycle Proteins / Q000502:physiology; D003198:Computer Simulation; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D005656:Fungal Proteins / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D005800:Genes, Fungal / Q000502:physiology*; D049770:Genes, Mating Type, Fungal; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D008954:Models, Biological; D043563:Receptors, Pheromone / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D012724:Sex Attractants / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; C081353:FAR1 protein, S cerevisiae; D005656:Fungal Proteins; D043563:Receptors, Pheromone; D012097:Repressor Proteins; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012724:Sex Attractants; D014157:Transcription Factors; C075580:FUS3 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins