A systems-biology analysis of feedback inhibition in the Sho1 osmotic-stress-response pathway.
Curr Biol
; 17(8): 659-67, 2007 Apr 17.
Article
en En
| MEDLINE
| ID: mdl-17363249
ABSTRACT
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.
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Bases de datos:
MEDLINE
Asunto principal:
Presión Osmótica
/
Saccharomyces cerevisiae
/
Transducción de Señal
/
Proteínas de Saccharomyces cerevisiae
/
Retroalimentación Fisiológica
/
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Curr Biol
Asunto de la revista:
BIOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos