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A systems-biology analysis of feedback inhibition in the Sho1 osmotic-stress-response pathway.

BACKGROUND: A common property of signal transduction systems is that they rapidly lose their ability to respond to a given stimulus. For instance in yeast, the mitogen-activated protein (MAP) kinase Hog1 is activated and inactivated within minutes, even when the osmotic-stress stimulus is sustained. RESULTS: Here, we used a combination of experimental and computational analyses to investigate the dynamic behavior of Hog1 activation in vivo. Computational modeling suggested that a negative-feedback loop operates early in the pathway and leads to rapid attenuation of Hog1 signaling. Experimental analysis revealed that the membrane-bound osmosensor Sho1 is phosphorylated by Hog1 and that phosphorylation occurs on Ser-166. Moreover, Sho1 exists in a homo-oligomeric complex, and phosphorylation by Hog1 promotes a transition from the oligomeric to monomeric state. A phosphorylation-site mutation (Sho1(S166E)) diminishes the formation of Sho1-oligomers, dampens activation of the Hog1 kinase, and impairs growth in high-salt or sorbitol conditions. CONCLUSIONS: These findings reveal a novel phosphorylation-dependent feedback loop leading to diminished cellular responses to an osmotic-stress stimulus.

Pubmed ID: 17363249

Authors

  • Hao N
  • Behar M
  • Parnell SC
  • Torres MP
  • Borchers CH
  • Elston TC
  • Dohlman HG

Journal

Current biology : CB

Publication Data

April 17, 2007

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM073180
  • Agency: NIGMS NIH HHS, Id: R01 GM073180

Mesh Terms

  • Feedback, Physiological
  • Membrane Proteins
  • Mitogen-Activated Protein Kinases
  • Osmotic Pressure
  • Phosphorylation
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Signal Transduction
  • Systems Biology