Parallel feedback loops control the basal activity of the HOG MAPK signaling cascade

Hoda Sharifian, Fabienne Lampert, Klement Stojanovski, Sergi Regot, Stefania Vaga, Raymond Buser, Sung Sik Lee, Heinz Koeppl, Francesc Posas, Serge Pelet, Matthias Peter

Research output: Contribution to journalArticlepeer-review

Abstract

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. This journal is

Original languageEnglish (US)
Pages (from-to)412-422
Number of pages11
JournalIntegrative Biology (United Kingdom)
Volume7
Issue number4
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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