Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5

Autores
van Drogen, Frank; Mishra, Ranjan; Rudolf, Fabian; Walczak, Michal J.; Lee, Sung Sik; Reiter, Wolfgang; Hegemann, Björn; Pelet, Serge; Dohnal, Ilse; Binolfi, Andrés; Yudina, Zinaida; Selenko, Philipp; Wider, Gerhard; Ammerer, Gustav; Peter, Matthias
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cells continuously adapt cellular processes by integrating external and internal signals. In yeast, multiple stress signals regulate pheromone signaling to prevent mating under unfavorable conditions. However, the underlying crosstalk mechanisms remain poorly understood. Here, we show that mechanical stress activates Pkc1, which prevents lysis of pheromone-treated cells by inhibiting polarized growth. In vitro Pkc1 phosphorylates conserved residues within the RING-H2 domains of the scaffold proteins Far1 and Ste5, which are also phosphorylated in vivo. Interestingly, Pkc1 triggers dispersal of Ste5 from mating projections upon mechanically induced stress and during cell-cell fusion, leading to inhibition of the MAPK Fus3. Indeed, RING phosphorylation interferes with Ste5 membrane association by preventing binding to the receptor-linked Gβγ protein. Cells expressing nonphosphorylatable Ste5 undergo increased lysis upon mechanical stress and exhibit defects in cell-cell fusion during mating, which is exacerbated by simultaneous expression of nonphosphorylatable Far1. These results uncover a mechanical stress-triggered crosstalk mechanism modulating pheromone signaling, polarized growth, and cell-cell fusion during mating.
Fil: van Drogen, Frank. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Mishra, Ranjan. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Rudolf, Fabian. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Walczak, Michal J.. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Lee, Sung Sik. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Reiter, Wolfgang. Universidad de Viena; Austria
Fil: Hegemann, Björn. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Pelet, Serge. Universite de Lausanne; Suiza
Fil: Dohnal, Ilse. Universidad de Viena; Austria
Fil: Binolfi, Andrés. Leibniz-institut Für Molekulare Pharmakologie; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Yudina, Zinaida. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Selenko, Philipp. Leibniz-institut Für Molekulare Pharmakologie; Alemania
Fil: Wider, Gerhard. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Ammerer, Gustav. Universidad de Viena; Austria
Fil: Peter, Matthias. Eidgenössische Technische Hochschule Zürich; Suiza
Materia
PKC
STE5
NMR
MECHANICAL STRESS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/160854

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oai_identifier_str oai:ri.conicet.gov.ar:11336/160854
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5van Drogen, FrankMishra, RanjanRudolf, FabianWalczak, Michal J.Lee, Sung SikReiter, WolfgangHegemann, BjörnPelet, SergeDohnal, IlseBinolfi, AndrésYudina, ZinaidaSelenko, PhilippWider, GerhardAmmerer, GustavPeter, MatthiasPKCSTE5NMRMECHANICAL STRESShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cells continuously adapt cellular processes by integrating external and internal signals. In yeast, multiple stress signals regulate pheromone signaling to prevent mating under unfavorable conditions. However, the underlying crosstalk mechanisms remain poorly understood. Here, we show that mechanical stress activates Pkc1, which prevents lysis of pheromone-treated cells by inhibiting polarized growth. In vitro Pkc1 phosphorylates conserved residues within the RING-H2 domains of the scaffold proteins Far1 and Ste5, which are also phosphorylated in vivo. Interestingly, Pkc1 triggers dispersal of Ste5 from mating projections upon mechanically induced stress and during cell-cell fusion, leading to inhibition of the MAPK Fus3. Indeed, RING phosphorylation interferes with Ste5 membrane association by preventing binding to the receptor-linked Gβγ protein. Cells expressing nonphosphorylatable Ste5 undergo increased lysis upon mechanical stress and exhibit defects in cell-cell fusion during mating, which is exacerbated by simultaneous expression of nonphosphorylatable Far1. These results uncover a mechanical stress-triggered crosstalk mechanism modulating pheromone signaling, polarized growth, and cell-cell fusion during mating.Fil: van Drogen, Frank. Eidgenössische Technische Hochschule Zürich; SuizaFil: Mishra, Ranjan. Eidgenössische Technische Hochschule Zürich; SuizaFil: Rudolf, Fabian. Eidgenössische Technische Hochschule Zürich; SuizaFil: Walczak, Michal J.. Eidgenössische Technische Hochschule Zürich; SuizaFil: Lee, Sung Sik. Eidgenössische Technische Hochschule Zürich; SuizaFil: Reiter, Wolfgang. Universidad de Viena; AustriaFil: Hegemann, Björn. Eidgenössische Technische Hochschule Zürich; SuizaFil: Pelet, Serge. Universite de Lausanne; SuizaFil: Dohnal, Ilse. Universidad de Viena; AustriaFil: Binolfi, Andrés. Leibniz-institut Für Molekulare Pharmakologie; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Yudina, Zinaida. Eidgenössische Technische Hochschule Zürich; SuizaFil: Selenko, Philipp. Leibniz-institut Für Molekulare Pharmakologie; AlemaniaFil: Wider, Gerhard. Eidgenössische Technische Hochschule Zürich; SuizaFil: Ammerer, Gustav. Universidad de Viena; AustriaFil: Peter, Matthias. Eidgenössische Technische Hochschule Zürich; SuizaRockefeller University Press2019-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/160854van Drogen, Frank; Mishra, Ranjan; Rudolf, Fabian; Walczak, Michal J.; Lee, Sung Sik; et al.; Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5; Rockefeller University Press; The Journal of cell biology; 218; 9; 9-2019; 3117-31331540-8140CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://rupress.org/jcb/article-abstract/218/9/3117/120966/Mechanical-stress-impairs-pheromone-signaling-via?redirectedFrom=fulltextinfo:eu-repo/semantics/altIdentifier/doi/10.1083/jcb.201808161info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:15Zoai:ri.conicet.gov.ar:11336/160854instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:08:15.68CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
spellingShingle Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
van Drogen, Frank
PKC
STE5
NMR
MECHANICAL STRESS
title_short Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title_full Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title_fullStr Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title_full_unstemmed Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title_sort Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
dc.creator.none.fl_str_mv van Drogen, Frank
Mishra, Ranjan
Rudolf, Fabian
Walczak, Michal J.
Lee, Sung Sik
Reiter, Wolfgang
Hegemann, Björn
Pelet, Serge
Dohnal, Ilse
Binolfi, Andrés
Yudina, Zinaida
Selenko, Philipp
Wider, Gerhard
Ammerer, Gustav
Peter, Matthias
author van Drogen, Frank
author_facet van Drogen, Frank
Mishra, Ranjan
Rudolf, Fabian
Walczak, Michal J.
Lee, Sung Sik
Reiter, Wolfgang
Hegemann, Björn
Pelet, Serge
Dohnal, Ilse
Binolfi, Andrés
Yudina, Zinaida
Selenko, Philipp
Wider, Gerhard
Ammerer, Gustav
Peter, Matthias
author_role author
author2 Mishra, Ranjan
Rudolf, Fabian
Walczak, Michal J.
Lee, Sung Sik
Reiter, Wolfgang
Hegemann, Björn
Pelet, Serge
Dohnal, Ilse
Binolfi, Andrés
Yudina, Zinaida
Selenko, Philipp
Wider, Gerhard
Ammerer, Gustav
Peter, Matthias
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PKC
STE5
NMR
MECHANICAL STRESS
topic PKC
STE5
NMR
MECHANICAL STRESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cells continuously adapt cellular processes by integrating external and internal signals. In yeast, multiple stress signals regulate pheromone signaling to prevent mating under unfavorable conditions. However, the underlying crosstalk mechanisms remain poorly understood. Here, we show that mechanical stress activates Pkc1, which prevents lysis of pheromone-treated cells by inhibiting polarized growth. In vitro Pkc1 phosphorylates conserved residues within the RING-H2 domains of the scaffold proteins Far1 and Ste5, which are also phosphorylated in vivo. Interestingly, Pkc1 triggers dispersal of Ste5 from mating projections upon mechanically induced stress and during cell-cell fusion, leading to inhibition of the MAPK Fus3. Indeed, RING phosphorylation interferes with Ste5 membrane association by preventing binding to the receptor-linked Gβγ protein. Cells expressing nonphosphorylatable Ste5 undergo increased lysis upon mechanical stress and exhibit defects in cell-cell fusion during mating, which is exacerbated by simultaneous expression of nonphosphorylatable Far1. These results uncover a mechanical stress-triggered crosstalk mechanism modulating pheromone signaling, polarized growth, and cell-cell fusion during mating.
Fil: van Drogen, Frank. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Mishra, Ranjan. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Rudolf, Fabian. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Walczak, Michal J.. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Lee, Sung Sik. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Reiter, Wolfgang. Universidad de Viena; Austria
Fil: Hegemann, Björn. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Pelet, Serge. Universite de Lausanne; Suiza
Fil: Dohnal, Ilse. Universidad de Viena; Austria
Fil: Binolfi, Andrés. Leibniz-institut Für Molekulare Pharmakologie; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Yudina, Zinaida. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Selenko, Philipp. Leibniz-institut Für Molekulare Pharmakologie; Alemania
Fil: Wider, Gerhard. Eidgenössische Technische Hochschule Zürich; Suiza
Fil: Ammerer, Gustav. Universidad de Viena; Austria
Fil: Peter, Matthias. Eidgenössische Technische Hochschule Zürich; Suiza
description Cells continuously adapt cellular processes by integrating external and internal signals. In yeast, multiple stress signals regulate pheromone signaling to prevent mating under unfavorable conditions. However, the underlying crosstalk mechanisms remain poorly understood. Here, we show that mechanical stress activates Pkc1, which prevents lysis of pheromone-treated cells by inhibiting polarized growth. In vitro Pkc1 phosphorylates conserved residues within the RING-H2 domains of the scaffold proteins Far1 and Ste5, which are also phosphorylated in vivo. Interestingly, Pkc1 triggers dispersal of Ste5 from mating projections upon mechanically induced stress and during cell-cell fusion, leading to inhibition of the MAPK Fus3. Indeed, RING phosphorylation interferes with Ste5 membrane association by preventing binding to the receptor-linked Gβγ protein. Cells expressing nonphosphorylatable Ste5 undergo increased lysis upon mechanical stress and exhibit defects in cell-cell fusion during mating, which is exacerbated by simultaneous expression of nonphosphorylatable Far1. These results uncover a mechanical stress-triggered crosstalk mechanism modulating pheromone signaling, polarized growth, and cell-cell fusion during mating.
publishDate 2019
dc.date.none.fl_str_mv 2019-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/160854
van Drogen, Frank; Mishra, Ranjan; Rudolf, Fabian; Walczak, Michal J.; Lee, Sung Sik; et al.; Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5; Rockefeller University Press; The Journal of cell biology; 218; 9; 9-2019; 3117-3133
1540-8140
CONICET Digital
CONICET
url http://hdl.handle.net/11336/160854
identifier_str_mv van Drogen, Frank; Mishra, Ranjan; Rudolf, Fabian; Walczak, Michal J.; Lee, Sung Sik; et al.; Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5; Rockefeller University Press; The Journal of cell biology; 218; 9; 9-2019; 3117-3133
1540-8140
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://rupress.org/jcb/article-abstract/218/9/3117/120966/Mechanical-stress-impairs-pheromone-signaling-via?redirectedFrom=fulltext
info:eu-repo/semantics/altIdentifier/doi/10.1083/jcb.201808161
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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