1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility

ERK1/2 mitogen-activated protein kinases (ERK) are key regulators of basic cellular processes, including proliferation, survival, and migration. Upon phosphorylation, ERK becomes activated and a portion of it dimerizes. The importance of ERK activation in specific cellular events is generally well d...

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Autores: de la Fuente-Vivas, Dalia, Cappitelli, Vincenzo, García-Gómez, Rocío, Valero-Díaz, Sara, Amato, Camilla, Rodriguéz, Javier, Duro Sánchez, Santiago|||0000-0002-3829-7562, von Kriegsheim, Alexander, Grusch, Michael|||0000-0001-5486-9340, Lozano, José, Arribas, Joaquín V|||0000-0002-0504-0664, Casar, Berta|||0000-0002-3058-5631, Crespo, Piero|||0000-0003-2825-7783
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:307963
Acesso em linha:https://ddd.uab.cat/record/307963
https://dx.doi.org/urn:doi:10.1002/1878-0261.13732
Access Level:acceso abierto
Palavra-chave:Cell motility
ERK
KSR
MAP kinases
Scaffold proteins
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spelling 1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motilityde la Fuente-Vivas, DaliaCappitelli, VincenzoGarcía-Gómez, RocíoValero-Díaz, SaraAmato, CamillaRodriguéz, JavierDuro Sánchez, Santiago|||0000-0002-3829-7562von Kriegsheim, AlexanderGrusch, Michael|||0000-0001-5486-9340Lozano, JoséArribas, Joaquín V|||0000-0002-0504-0664Casar, Berta|||0000-0002-3058-5631Crespo, Piero|||0000-0003-2825-7783Cell motilityERKKSRMAP kinasesScaffold proteinsERK1/2 mitogen-activated protein kinases (ERK) are key regulators of basic cellular processes, including proliferation, survival, and migration. Upon phosphorylation, ERK becomes activated and a portion of it dimerizes. The importance of ERK activation in specific cellular events is generally well documented, but the role played by dimerization is largely unknown. Here, we demonstrate that impeding ERK dimerization precludes cellular movement by interfering with the molecular machinery that executes the rearrangements of the actin cytoskeleton. We also show that a constitutively dimeric ERK mutant can drive cell motility per se, demonstrating that ERK dimerization is both necessary and sufficient for inducing cellular migration. Importantly, we unveil that the scaffold protein kinase suppressor of Ras 1 (KSR1) is a critical element for endowing external agonists, acting through tyrosine kinase receptors, with the capacity to induce ERK dimerization and, subsequently, to unleash cellular motion. In agreement, clinical data disclose that high KSR1 expression levels correlate with greater metastatic potential and adverse evolution of mammary tumors. Overall, our results portray both ERK dimerization and KSR1 as essential factors for the regulation of cell motility and mammary tumor dissemination. In mammary tumor cells, ERK dimerization is both necessary and sufficient for inducing cellular migration. The scaffold protein KSR1 is a critical element for endowing external agonists, acting through tyrosine kinase receptors, with the capacity to induce ERK dimerization and, subsequently, unleashing cellular motion, as a consequence of which tumor cell migration and metastatic dissemination are promoted.Hospital Universitari Vall d'Hebron 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/307963https://dx.doi.org/urn:doi:10.1002/1878-0261.13732reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI22/00001Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PDC2022-133569-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-126288OB-I00Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CB16/12/00436open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3079632026-06-06T12:50:31Z
dc.title.none.fl_str_mv 1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility
title 1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility
spellingShingle 1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility
de la Fuente-Vivas, Dalia
Cell motility
ERK
KSR
MAP kinases
Scaffold proteins
title_short 1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility
title_full 1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility
title_fullStr 1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility
title_full_unstemmed 1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility
title_sort 1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility
dc.creator.none.fl_str_mv de la Fuente-Vivas, Dalia
Cappitelli, Vincenzo
García-Gómez, Rocío
Valero-Díaz, Sara
Amato, Camilla
Rodriguéz, Javier
Duro Sánchez, Santiago|||0000-0002-3829-7562
von Kriegsheim, Alexander
Grusch, Michael|||0000-0001-5486-9340
Lozano, José
Arribas, Joaquín V|||0000-0002-0504-0664
Casar, Berta|||0000-0002-3058-5631
Crespo, Piero|||0000-0003-2825-7783
author de la Fuente-Vivas, Dalia
author_facet de la Fuente-Vivas, Dalia
Cappitelli, Vincenzo
García-Gómez, Rocío
Valero-Díaz, Sara
Amato, Camilla
Rodriguéz, Javier
Duro Sánchez, Santiago|||0000-0002-3829-7562
von Kriegsheim, Alexander
Grusch, Michael|||0000-0001-5486-9340
Lozano, José
Arribas, Joaquín V|||0000-0002-0504-0664
Casar, Berta|||0000-0002-3058-5631
Crespo, Piero|||0000-0003-2825-7783
author_role author
author2 Cappitelli, Vincenzo
García-Gómez, Rocío
Valero-Díaz, Sara
Amato, Camilla
Rodriguéz, Javier
Duro Sánchez, Santiago|||0000-0002-3829-7562
von Kriegsheim, Alexander
Grusch, Michael|||0000-0001-5486-9340
Lozano, José
Arribas, Joaquín V|||0000-0002-0504-0664
Casar, Berta|||0000-0002-3058-5631
Crespo, Piero|||0000-0003-2825-7783
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Hospital Universitari Vall d'Hebron
dc.subject.none.fl_str_mv Cell motility
ERK
KSR
MAP kinases
Scaffold proteins
topic Cell motility
ERK
KSR
MAP kinases
Scaffold proteins
description ERK1/2 mitogen-activated protein kinases (ERK) are key regulators of basic cellular processes, including proliferation, survival, and migration. Upon phosphorylation, ERK becomes activated and a portion of it dimerizes. The importance of ERK activation in specific cellular events is generally well documented, but the role played by dimerization is largely unknown. Here, we demonstrate that impeding ERK dimerization precludes cellular movement by interfering with the molecular machinery that executes the rearrangements of the actin cytoskeleton. We also show that a constitutively dimeric ERK mutant can drive cell motility per se, demonstrating that ERK dimerization is both necessary and sufficient for inducing cellular migration. Importantly, we unveil that the scaffold protein kinase suppressor of Ras 1 (KSR1) is a critical element for endowing external agonists, acting through tyrosine kinase receptors, with the capacity to induce ERK dimerization and, subsequently, to unleash cellular motion. In agreement, clinical data disclose that high KSR1 expression levels correlate with greater metastatic potential and adverse evolution of mammary tumors. Overall, our results portray both ERK dimerization and KSR1 as essential factors for the regulation of cell motility and mammary tumor dissemination. In mammary tumor cells, ERK dimerization is both necessary and sufficient for inducing cellular migration. The scaffold protein KSR1 is a critical element for endowing external agonists, acting through tyrosine kinase receptors, with the capacity to induce ERK dimerization and, subsequently, unleashing cellular motion, as a consequence of which tumor cell migration and metastatic dissemination are promoted.
publishDate 2024
dc.date.none.fl_str_mv 2
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/307963
https://dx.doi.org/urn:doi:10.1002/1878-0261.13732
url https://ddd.uab.cat/record/307963
https://dx.doi.org/urn:doi:10.1002/1878-0261.13732
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI22/00001
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PDC2022-133569-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-126288OB-I00
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CB16/12/00436
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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