Robustness and fragility in the yeast high osmolarity glycerol (HOG) signal-transduction pathway.
Artikel i vetenskaplig tidskrift, 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
Författare
Marcus Krantz
Göteborgs universitet
Doryaneh Ahmadpour
Göteborgs universitet
Lars-Göran Ottosson
Göteborgs universitet
Jonas Warringer
Göteborgs universitet
Christian Waltermann
Bodil Nordlander
Göteborgs universitet
Edda Klipp
Anders Blomberg
Göteborgs universitet
Stefan Hohmann
Göteborgs universitet
Hiroaki Kitano
Molecular Systems Biology
1744-4292 (ISSN)
Vol. 5 281-Ämneskategorier
Cellbiologi
Biokemi och molekylärbiologi
DOI
10.1038/msb.2009.36
PubMed
19536204