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| Pàgina inicial > Articles > Articles publicats > 1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility |
(Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Medical University of Vienna) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universidad de Cantabria) (Universidad de Cantabria)| Data: | 2024 |
| Resum: | 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. |
| Ajuts: | Instituto de Salud Carlos III PI22/00001 Agencia Estatal de Investigación PDC2022-133569-I00 Agencia Estatal de Investigación PID2021-126288OB-I00 Ministerio de Economía y Competitividad CB16/12/00436 |
| Drets: | Aquest 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.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Cell motility ; ERK ; KSR ; MAP kinases ; Scaffold proteins |
| Publicat a: | Molecular oncology, Vol. 19 (september 2024) , p. 452-473, ISSN 1878-0261 |
