Robustness and fragility in the yeast high osmolarity glycerol (HOG) signal-transduction pathway.
Journal article, 2009
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.
Physiological
metabolism
Osmolar Concentration
physiology
Stress
metabolism
metabolism
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
physiology
Mitogen-Activated Protein Kinases
Computer Simulation
Cluster Analysis
Models
Signal Transduction
Biological
physiology
Author
Marcus Krantz
University of Gothenburg
Doryaneh Ahmadpour
University of Gothenburg
Lars-Göran Ottosson
University of Gothenburg
Jonas Warringer
University of Gothenburg
Christian Waltermann
Bodil Nordlander
University of Gothenburg
Edda Klipp
Anders Blomberg
University of Gothenburg
Stefan Hohmann
University of Gothenburg
Hiroaki Kitano
Molecular Systems Biology
17444292 (eISSN)
Vol. 5 281-Subject Categories
Cell Biology
Biochemistry and Molecular Biology
DOI
10.1038/msb.2009.36
PubMed
19536204