title: A quantitative study of the Hog1 MAPK response to fluctuating osmotic stress in Saccharomyces cerevisiae.
abstract: BACKGROUND
  Yeast cells live in a highly fluctuating environment with respect to temperature, nutrients, and especially osmolarity. The Hog1 mitogen-activated protein kinase (MAPK) pathway is crucial for the adaption of yeast cells to external osmotic changes.
  
  
  RESULTS
  To better understand the osmo-adaption mechanism in the budding yeast Saccharomyces cerevisiae, we have developed a mathematical model and quantitatively investigated the Hog1 response to osmotic stress. The model agrees well with various experimental data for the Hog1 response to different types of osmotic changes. Kinetic analyses of the model indicate that budding yeast cells have evolved to protect themselves economically: while they show almost no response to fast pulse-like changes of osmolarity, they respond periodically and are well-adapted to osmotic changes with a certain frequency. To quantify the signal transduction efficiency of the osmo-adaption network, we introduced a measure of the signal response gain, which is defined as the ratio of output change integral to input (signal) change integral. Model simulations indicate that the Hog1 response gain shows bell-shaped response curves with respect to the duration of a single osmotic pulse and to the frequency of periodic square osmotic pulses, while for up-staircase (ramp) osmotic changes, the gain depends on the slope.
  
  
  CONCLUSIONS
  The model analyses suggest that budding yeast cells have selectively evolved to be optimized to some specific types of osmotic changes. In addition, our work implies that the signaling output can be dynamically controlled by fine-tuning the signal input profiles.
authors.affiliation: Centre for Biological Signalling Studies (bioss), University of Freiburg, Freiburg, Germany. zhike.zi@bioss.uni-freiburg.de
authors.forename: Zhike
authors.initials: Z
authors.lastname: Zi
authors.forename: Wolfram
authors.initials: W
authors.lastname: Liebermeister
authors.forename: Edda
authors.initials: E
authors.lastname: Klipp
mesh_terms: D000465:Algorithms; D002467:Cell Nucleus / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins / Q000737:chemistry; D007700:Kinetics; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D015233:Models, Statistical; D008962:Models, Theoretical; D009995:Osmosis; D009997:Osmotic Pressure; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases