Interaction Dynamics Determine Signaling and Output Pathway Responses
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 pr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717303613 |
| _version_ | 1818943740522266624 |
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| author | Klement Stojanovski Tony Ferrar Hannah Benisty Friedemann Uschner Javier Delgado Javier Jimenez Carme Solé Eulalia de Nadal Edda Klipp Francesc Posas Luis Serrano Christina Kiel |
| author_facet | Klement Stojanovski Tony Ferrar Hannah Benisty Friedemann Uschner Javier Delgado Javier Jimenez Carme Solé Eulalia de Nadal Edda Klipp Francesc Posas Luis Serrano Christina Kiel |
| author_sort | Klement Stojanovski |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T07:32:08Z |
| format | Article |
| id | doaj.art-5b31b98c109b4be7825a4ebde1dd8571 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T07:32:08Z |
| publishDate | 2017-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5b31b98c109b4be7825a4ebde1dd85712022-12-21T19:48:24ZengElsevierCell Reports2211-12472017-04-0119113614910.1016/j.celrep.2017.03.029Interaction Dynamics Determine Signaling and Output Pathway ResponsesKlement Stojanovski0Tony Ferrar1Hannah Benisty2Friedemann Uschner3Javier Delgado4Javier Jimenez5Carme Solé6Eulalia de Nadal7Edda Klipp8Francesc Posas9Luis Serrano10Christina Kiel11Cell Signaling Research Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, SpainEMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, SpainEMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, SpainTheoretical Biophysics, Humboldt-Universität zu Berlin, 10115 Berlin, GermanyEMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, SpainCell Signaling Research Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, SpainCell Signaling Research Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, SpainCell Signaling Research Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, SpainTheoretical Biophysics, Humboldt-Universität zu Berlin, 10115 Berlin, GermanyCell Signaling Research Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, SpainEMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, SpainEMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, SpainThe 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.http://www.sciencedirect.com/science/article/pii/S2211124717303613kinetic perturbationsphosphorelayHOG-MAPK pathwayosmostress response |
| spellingShingle | Klement Stojanovski Tony Ferrar Hannah Benisty Friedemann Uschner Javier Delgado Javier Jimenez Carme Solé Eulalia de Nadal Edda Klipp Francesc Posas Luis Serrano Christina Kiel Interaction Dynamics Determine Signaling and Output Pathway Responses Cell Reports kinetic perturbations phosphorelay HOG-MAPK pathway osmostress response |
| title | Interaction Dynamics Determine Signaling and Output Pathway Responses |
| title_full | Interaction Dynamics Determine Signaling and Output Pathway Responses |
| title_fullStr | Interaction Dynamics Determine Signaling and Output Pathway Responses |
| title_full_unstemmed | Interaction Dynamics Determine Signaling and Output Pathway Responses |
| title_short | Interaction Dynamics Determine Signaling and Output Pathway Responses |
| title_sort | interaction dynamics determine signaling and output pathway responses |
| topic | kinetic perturbations phosphorelay HOG-MAPK pathway osmostress response |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717303613 |
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