Cargando…
Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling
Mitogen-activated protein kinases (MAPK): Erk1 and Erk2 are key players in negative-feedback regulation of fibroblast growth factor (FGF) signaling. Upon activation, Erk1 and Erk2 directly phosphorylate FGF receptor 1 (FGFR1) at a specific serine residue in the C-terminal part of the receptor, subst...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514807/ https://www.ncbi.nlm.nih.gov/pubmed/31013829 http://dx.doi.org/10.3390/ijms20081826 |
_version_ | 1783417945887604736 |
---|---|
author | Zakrzewska, Malgorzata Opalinski, Lukasz Haugsten, Ellen M. Otlewski, Jacek Wiedlocha, Antoni |
author_facet | Zakrzewska, Malgorzata Opalinski, Lukasz Haugsten, Ellen M. Otlewski, Jacek Wiedlocha, Antoni |
author_sort | Zakrzewska, Malgorzata |
collection | PubMed |
description | Mitogen-activated protein kinases (MAPK): Erk1 and Erk2 are key players in negative-feedback regulation of fibroblast growth factor (FGF) signaling. Upon activation, Erk1 and Erk2 directly phosphorylate FGF receptor 1 (FGFR1) at a specific serine residue in the C-terminal part of the receptor, substantially reducing the tyrosine phosphorylation in the receptor kinase domain and its signaling. Similarly, active Erks can also phosphorylate multiple threonine residues in the docking protein FGF receptor substrate 2 (FRS2), a major mediator of FGFR signaling. Here, we demonstrate that in NIH3T3 mouse fibroblasts and human osteosarcoma U2OS cells stably expressing FGFR1, in addition to Erk1 and Erk2, p38 kinase is able to phosphorylate FRS2. Simultaneous inhibition of Erk1/2 and p38 kinase led to a significant change in the phosphorylation pattern of FRS2 that in turn resulted in prolonged tyrosine phosphorylation of FGFR1 and FRS2 and in sustained signaling, as compared to the selective inhibition of Erks. Furthermore, excessive activation of p38 with anisomycin partially compensated the lack of Erks activity. These experiments reveal a novel crosstalk between p38 and Erk1/2 in downregulation of FGF-induced signaling. |
format | Online Article Text |
id | pubmed-6514807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65148072019-05-30 Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling Zakrzewska, Malgorzata Opalinski, Lukasz Haugsten, Ellen M. Otlewski, Jacek Wiedlocha, Antoni Int J Mol Sci Communication Mitogen-activated protein kinases (MAPK): Erk1 and Erk2 are key players in negative-feedback regulation of fibroblast growth factor (FGF) signaling. Upon activation, Erk1 and Erk2 directly phosphorylate FGF receptor 1 (FGFR1) at a specific serine residue in the C-terminal part of the receptor, substantially reducing the tyrosine phosphorylation in the receptor kinase domain and its signaling. Similarly, active Erks can also phosphorylate multiple threonine residues in the docking protein FGF receptor substrate 2 (FRS2), a major mediator of FGFR signaling. Here, we demonstrate that in NIH3T3 mouse fibroblasts and human osteosarcoma U2OS cells stably expressing FGFR1, in addition to Erk1 and Erk2, p38 kinase is able to phosphorylate FRS2. Simultaneous inhibition of Erk1/2 and p38 kinase led to a significant change in the phosphorylation pattern of FRS2 that in turn resulted in prolonged tyrosine phosphorylation of FGFR1 and FRS2 and in sustained signaling, as compared to the selective inhibition of Erks. Furthermore, excessive activation of p38 with anisomycin partially compensated the lack of Erks activity. These experiments reveal a novel crosstalk between p38 and Erk1/2 in downregulation of FGF-induced signaling. MDPI 2019-04-12 /pmc/articles/PMC6514807/ /pubmed/31013829 http://dx.doi.org/10.3390/ijms20081826 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Zakrzewska, Malgorzata Opalinski, Lukasz Haugsten, Ellen M. Otlewski, Jacek Wiedlocha, Antoni Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling |
title | Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling |
title_full | Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling |
title_fullStr | Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling |
title_full_unstemmed | Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling |
title_short | Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling |
title_sort | crosstalk between p38 and erk 1/2 in downregulation of fgf1-induced signaling |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514807/ https://www.ncbi.nlm.nih.gov/pubmed/31013829 http://dx.doi.org/10.3390/ijms20081826 |
work_keys_str_mv | AT zakrzewskamalgorzata crosstalkbetweenp38anderk12indownregulationoffgf1inducedsignaling AT opalinskilukasz crosstalkbetweenp38anderk12indownregulationoffgf1inducedsignaling AT haugstenellenm crosstalkbetweenp38anderk12indownregulationoffgf1inducedsignaling AT otlewskijacek crosstalkbetweenp38anderk12indownregulationoffgf1inducedsignaling AT wiedlochaantoni crosstalkbetweenp38anderk12indownregulationoffgf1inducedsignaling |