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Robustness and frag...
Robustness and fragility in the high osmolarity glycerol (HOG) pathway in S. cerevisiae
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- Krantz, Marcus, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för cell- och molekylärbiologi,Department of Cell and Molecular Biology,University of Gothenburg
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- Ahmadpour, Doryaneh, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för cell- och molekylärbiologi,Department of Cell and Molecular Biology,University of Gothenburg
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- Ottosson, Lars-Göran (author)
- Gothenburg University,Göteborgs universitet,Institutionen för cell- och molekylärbiologi,Department of Cell and Molecular Biology,University of Gothenburg
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- Warringer, Jonas, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för cell- och molekylärbiologi,Department of Cell and Molecular Biology,University of Gothenburg
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Waltermann, Christian (author)
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- Nordlander, Bodil, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för cell- och molekylärbiologi,Department of Cell and Molecular Biology,University of Gothenburg
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Klipp, Edda (author)
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- Blomberg, Anders, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för cell- och molekylärbiologi,Department of Cell and Molecular Biology,University of Gothenburg
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- Hohmann, Stefan, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för cell- och molekylärbiologi,Department of Cell and Molecular Biology,University of Gothenburg
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Kitano, Hiroaki (author)
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(creator_code:org_t)
- 2009
- 2009
- English.
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In: 10th International Conference on Systems Biology (ICSB2009) proceedings, 10th International Conference on Systems Biology (ICSB2009), Aug 30 - Sep 4, Stanford, California, USA.
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Abstract
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- Cellular signalling networks integrate environmental stimuli with information on cellular status. These networks must be robust against stochastic fluctuations in external stimuli as well as in the amounts of signalling components. Here [1], we challenge the yeast HOG signal transduction pathway with systematic perturbations in components’ expression levels implemented by a “genetic tug-of-war” methodology under various external conditions in search of nodes of fragilities. We observe a substantially higher frequency of fragile nodes in this signal transduction pathway than has been observed for other cellular processes. These fragilities disperse without any clear pattern over biochemical functions or location in pathway topology, with the most sensitive nodes being the proteins PBS2 and SSK1. They are also largely independent of pathway activation by external stimuli. However, the strongest toxicities are caused by pathway hyperactivation. We studied the influence of seven regulatory motifs around these HOG pathway components in silico through ODE models. Based on the SLN1 and the MAPK modules of a mathematical model of osmoregulation in budding yeast by Klipp et al. [2] we included new motifs and fitted the affected parameters to time courses of dually phosphorylated Hog1p generated by the original model under stress and stress-free conditions. The regulations taken into account by our analysis include Pbs2p scaffolding, Ssk1p and Pbs2p autoactivation, and the formation of a stable dimer between Ssk2p and Ssk1p. A subsequent sensitivity analysis identified Pbs2's role as a scaffold protein and Ssk1p-Ssk2p dimerization as the important contributors to the observed robustness pattern in silico. Thus, in vivo robustness data can be used to discriminate and improve mathematical models.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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To the university's database
- By the author/editor
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Krantz, Marcus, ...
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Ahmadpour, Dorya ...
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Ottosson, Lars-G ...
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Warringer, Jonas ...
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Waltermann, Chri ...
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Nordlander, Bodi ...
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Klipp, Edda
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Blomberg, Anders ...
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Hohmann, Stefan, ...
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Kitano, Hiroaki
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
- 10th Internation ...
- By the university
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University of Gothenburg
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Chalmers University of Technology