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Cell Rep. 2017 Apr 4;19(1):136-149. doi: 10.1016/j.celrep.2017.03.029.

Interaction Dynamics Determine Signaling and Output Pathway Responses.

Author information

1
Cell Signaling Research Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
2
EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra, 08003 Barcelona, Spain.
3
Theoretical Biophysics, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.
4
Cell Signaling Research Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain. Electronic address: francesc.posas@upf.edu.
5
EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra, 08003 Barcelona, Spain; ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain. Electronic address: luis.serrano@crg.eu.
6
EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra, 08003 Barcelona, Spain. Electronic address: christina.kiel@crg.eu.

Abstract

The understanding of interaction dynamics in signaling pathways can shed light on pathway architecture and provide insights into targets for intervention. Here, we explored the relevance of kinetic rate constants of a key upstream osmosensor in the yeast high-osmolarity glycerol-mitogen-activated protein kinase (HOG-MAPK) pathway to signaling output responses. We created mutant pairs of the Sln1-Ypd1 complex interface that caused major compensating changes in the association (kon) and dissociation (koff) rate constants (kinetic perturbations) but only moderate changes in the overall complex affinity (Kd). Yeast cells carrying a Sln1-Ypd1 mutant pair with moderate increases in kon and koff displayed a lower threshold of HOG pathway activation than wild-type cells. Mutants with higher kon and koff rates gave rise to higher basal signaling and gene expression but impaired osmoadaptation. Thus, the kon and koff rates of the components in the Sln1 osmosensor determine proper signaling dynamics and osmoadaptation.

KEYWORDS:

HOG-MAPK pathway; kinetic perturbations; osmostress response; phosphorelay

PMID:
28380353
DOI:
10.1016/j.celrep.2017.03.029
[Indexed for MEDLINE]
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