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