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Phosphoproteomic analyses reveal novel cross-modulation mechanisms between two signaling pathways in yeast.

Vaga S, Bernardo-Faura M, Cokelaer T, Maiolica A, Barnes CA, Gillet LC, Hegemann B, van Drogen F, Sharifian H, Klipp E, Peter M, Saez-Rodriguez J, Aebersold R - Mol. Syst. Biol. (2014)

Bottom Line: We observed a pheromone-induced down-regulation of Hog1 phosphorylation due to Gpd1, Ste20, Ptp2, Pbs2, and Ptc1.Distinct Ste20 and Pbs2 phosphosites responded differently to the two stimuli, suggesting these proteins as key mediators of the information exchange.Our results show that the integration of the response to different stimuli requires complex interconnections between signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Institute of Molecular Systems Biology ETH Zürich, Zürich, Switzerland.

No MeSH data available.


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Hypothesis validation by logic modeling
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fig08: Hypothesis validation by logic modeling

Mentions: To test some of the novel mechanisms described above, we then developed a set of modified versions of our logic model either by implementing Ste20_T511 as the main Ste20 P-pep mediating crosstalk (Fig7E), and/or by introducing the double-negative inhibition between ppGpd1 and ppHog1. The model including both proposed mechanisms consisted of 39 nodes and 73 interactions (Fig8A). Since a common formalism to build dynamic models is ODEs (Kholodenko et al, 2010), we next transformed our logic models into logic ODEs (Wittmann et al, 2009) by means of CellNOpt (Terfve et al, 2012). For details regarding P-pep modeling, please see Materials and Methods. We then trained all the resulting models, within CellNOpt, to the three time course data corresponding to the stimulation with NaCl only, pheromone only, and both stimuli at the same time, that is, the first row, the first column, and the diagonal of the stimulation matrix (Fig1B), respectively.


Phosphoproteomic analyses reveal novel cross-modulation mechanisms between two signaling pathways in yeast.

Vaga S, Bernardo-Faura M, Cokelaer T, Maiolica A, Barnes CA, Gillet LC, Hegemann B, van Drogen F, Sharifian H, Klipp E, Peter M, Saez-Rodriguez J, Aebersold R - Mol. Syst. Biol. (2014)

Hypothesis validation by logic modeling
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300490&req=5

fig08: Hypothesis validation by logic modeling
Mentions: To test some of the novel mechanisms described above, we then developed a set of modified versions of our logic model either by implementing Ste20_T511 as the main Ste20 P-pep mediating crosstalk (Fig7E), and/or by introducing the double-negative inhibition between ppGpd1 and ppHog1. The model including both proposed mechanisms consisted of 39 nodes and 73 interactions (Fig8A). Since a common formalism to build dynamic models is ODEs (Kholodenko et al, 2010), we next transformed our logic models into logic ODEs (Wittmann et al, 2009) by means of CellNOpt (Terfve et al, 2012). For details regarding P-pep modeling, please see Materials and Methods. We then trained all the resulting models, within CellNOpt, to the three time course data corresponding to the stimulation with NaCl only, pheromone only, and both stimuli at the same time, that is, the first row, the first column, and the diagonal of the stimulation matrix (Fig1B), respectively.

Bottom Line: We observed a pheromone-induced down-regulation of Hog1 phosphorylation due to Gpd1, Ste20, Ptp2, Pbs2, and Ptc1.Distinct Ste20 and Pbs2 phosphosites responded differently to the two stimuli, suggesting these proteins as key mediators of the information exchange.Our results show that the integration of the response to different stimuli requires complex interconnections between signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Institute of Molecular Systems Biology ETH Zürich, Zürich, Switzerland.

No MeSH data available.


Related in: MedlinePlus