Robustness and fragility in the yeast high osmolarity glycerol (HOG) signal-transduction pathway

Mol Syst Biol. 2009;5:281. doi: 10.1038/msb.2009.36. Epub 2009 Jun 16.

Abstract

Cellular signalling networks integrate environmental stimuli with the information on cellular status. These networks must be robust against stochastic fluctuations in stimuli as well as in the amounts of signalling components. Here, we challenge the yeast HOG signal-transduction pathway with systematic perturbations in components' expression levels under various external conditions in search for nodes of fragility. We observe a substantially higher frequency of fragile nodes in this signal-transduction pathway than that has been observed for other cellular processes. These fragilities disperse without any clear pattern over biochemical functions or location in pathway topology and they are largely independent of pathway activation by external stimuli. However, the strongest toxicities are caused by pathway hyperactivation. In silico analysis highlights the impact of model structure on in silico robustness, and suggests complex formation and scaffolding as important contributors to the observed fragility patterns. Thus, in vivo robustness data can be used to discriminate and improve mathematical models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • Computer Simulation
  • Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinases / physiology*
  • Models, Biological
  • Osmolar Concentration
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Signal Transduction
  • Stress, Physiological

Substances

  • Saccharomyces cerevisiae Proteins
  • HOG1 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases