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
Jazyk: angličtina
Rok vydání: 2015
Předmět:
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