Parallel feedback loops control the basal activity of the HOG MAPK signaling cascade
Autor: | Hoda Sharifian, Matthias Peter, Sung Sik Lee, Serge Pelet, Sergi Regot, Klement Stojanovski, Heinz Koeppl, Francesc Posas, Stefania Vaga, Fabienne Lampert, Raymond Buser |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Saccharomyces cerevisiae Proteins
MAP Kinase Signaling System Saccharomyces cerevisiae Cell Mutant Biophysics Biochemistry Models Biological 03 medical and health sciences Basal (phylogenetics) Osmoregulation Osmotic Pressure medicine Computer Simulation 030304 developmental biology Feedback Physiological 0303 health sciences biology Osmotic concentration Kinase 030302 biochemistry & molecular biology biology.organism_classification Cell biology medicine.anatomical_structure Glucose Mitogen-activated protein kinase Glucosa biology.protein Saccharomyces cerevisiae -- Metabolisme Phosphorylation Mitogen-Activated Protein Kinases |
Zdroj: | Integrative Biology Integrative Biology, 7 (4) Recercat. Dipósit de la Recerca de Catalunya instname Europe PubMed Central Integrative biology : quantitative biosciences from nano to macro |
ISSN: | 1757-9694 1757-9708 |
DOI: | 10.3929/ethz-b-000100587 |
Popis: | Tight regulation of the MAP kinase Hog1 is crucial for survival under changing osmotic conditions. Interestingly, we found that Hog1 phosphorylates multiple upstream components, implying feedback regulation within the signaling cascade. Taking advantage of an unexpected link between glucose availability and Hog1 activity, we used quantitative single cell measurements and computational modeling to unravel feedback regulation operating in addition to the well-known adaptation feedback triggered by glycerol accumulation. Indeed, we found that Hog1 phosphorylates its activating kinase Ssk2 on several sites, and cells expressing a non-phosphorylatable Ssk2 mutant are partially defective for feedback regulation and proper control of basal Hog1 activity. Together, our data suggest that Hog1 activity is controlled by intertwined regulatory mechanisms operating with varying kinetics, which together tune the Hog1 response to balance basal Hog1 activity and its steady-state level after adaptation to high osmolarity. Integrative Biology, 7 (4) ISSN:1757-9694 ISSN:1757-9708 |
Databáze: | OpenAIRE |
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