ERK1/2 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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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13732 |
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| author | Dalia de laFuente‐Vivas Vincenzo Cappitelli Rocío García‐Gómez Sara Valero‐Díaz Camilla Amato Javier Rodriguéz Santiago Duro‐Sánchez Alexander vonKriegsheim Michael Grusch José Lozano Joaquín Arribas Berta Casar Piero Crespo |
| author_facet | Dalia de laFuente‐Vivas Vincenzo Cappitelli Rocío García‐Gómez Sara Valero‐Díaz Camilla Amato Javier Rodriguéz Santiago Duro‐Sánchez Alexander vonKriegsheim Michael Grusch José Lozano Joaquín Arribas Berta Casar Piero Crespo |
| author_sort | Dalia de laFuente‐Vivas |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-88947603665a4e1eae2593946fc70db4 |
| institution | Kabale University |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-88947603665a4e1eae2593946fc70db42025-02-04T17:30:20ZengWileyMolecular Oncology1574-78911878-02612025-02-0119245247310.1002/1878-0261.13732ERK1/2 mitogen‐activated protein kinase dimerization is essential for the regulation of cell motilityDalia de laFuente‐Vivas0Vincenzo Cappitelli1Rocío García‐Gómez2Sara Valero‐Díaz3Camilla Amato4Javier Rodriguéz5Santiago Duro‐Sánchez6Alexander vonKriegsheim7Michael Grusch8José Lozano9Joaquín Arribas10Berta Casar11Piero Crespo12Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC) Consejo Superior de Investigaciones Científicas (CSIC) – Universidad de Cantabria Santander SpainInstituto de Biomedicina y Biotecnología de Cantabria (IBBTEC) Consejo Superior de Investigaciones Científicas (CSIC) – Universidad de Cantabria Santander SpainInstituto de Biomedicina y Biotecnología de Cantabria (IBBTEC) Consejo Superior de Investigaciones Científicas (CSIC) – Universidad de Cantabria Santander SpainInstituto de Biomedicina y Biotecnología de Cantabria (IBBTEC) Consejo Superior de Investigaciones Científicas (CSIC) – Universidad de Cantabria Santander SpainInstituto de Biomedicina y Biotecnología de Cantabria (IBBTEC) Consejo Superior de Investigaciones Científicas (CSIC) – Universidad de Cantabria Santander SpainCancer Research UK Scotland Centre, Institute of Genetics and Cancer University of Edinburgh UKCentro de Investigación Biomédica en Red de Cáncer (CIBERONC) Instituto de Salud Carlos III Madrid SpainCancer Research UK Scotland Centre, Institute of Genetics and Cancer University of Edinburgh UKCenter for Cancer Research Medical University of Vienna AustriaUniversidad de Málaga and Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina – IBIMA, Plataforma Bionand SpainCentro de Investigación Biomédica en Red de Cáncer (CIBERONC) Instituto de Salud Carlos III Madrid SpainInstituto de Biomedicina y Biotecnología de Cantabria (IBBTEC) Consejo Superior de Investigaciones Científicas (CSIC) – Universidad de Cantabria Santander SpainInstituto de Biomedicina y Biotecnología de Cantabria (IBBTEC) Consejo Superior de Investigaciones Científicas (CSIC) – Universidad de Cantabria Santander SpainERK1/2 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.https://doi.org/10.1002/1878-0261.13732cell motilityERKKSRMAP kinasesscaffold proteins |
| spellingShingle | Dalia de laFuente‐Vivas Vincenzo Cappitelli Rocío García‐Gómez Sara Valero‐Díaz Camilla Amato Javier Rodriguéz Santiago Duro‐Sánchez Alexander vonKriegsheim Michael Grusch José Lozano Joaquín Arribas Berta Casar Piero Crespo ERK1/2 mitogen‐activated protein kinase dimerization is essential for the regulation of cell motility Molecular Oncology cell motility ERK KSR MAP kinases scaffold proteins |
| title | ERK1/2 mitogen‐activated protein kinase dimerization is essential for the regulation of cell motility |
| title_full | ERK1/2 mitogen‐activated protein kinase dimerization is essential for the regulation of cell motility |
| title_fullStr | ERK1/2 mitogen‐activated protein kinase dimerization is essential for the regulation of cell motility |
| title_full_unstemmed | ERK1/2 mitogen‐activated protein kinase dimerization is essential for the regulation of cell motility |
| title_short | ERK1/2 mitogen‐activated protein kinase dimerization is essential for the regulation of cell motility |
| title_sort | erk1 2 mitogen activated protein kinase dimerization is essential for the regulation of cell motility |
| topic | cell motility ERK KSR MAP kinases scaffold proteins |
| url | https://doi.org/10.1002/1878-0261.13732 |
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