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Mek1 and Mek2 Functional Redundancy in Erythropoiesis
Several studies have established the crucial role of the extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase pathway in hematopoietic cell proliferation and differentiation. MEK1 and MEK2 phosphorylate and activate ERK1 and ERK2. However, whether MEK1 and MEK2 differentially...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353236/ https://www.ncbi.nlm.nih.gov/pubmed/34386488 http://dx.doi.org/10.3389/fcell.2021.639022 |
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author | Beuret, Laurent Fortier-Beaulieu, Simon-Pierre Rondeau, Vincent Roy, Sophie Houde, Nicolas Balabanian, Karl Espéli, Marion Charron, Jean |
author_facet | Beuret, Laurent Fortier-Beaulieu, Simon-Pierre Rondeau, Vincent Roy, Sophie Houde, Nicolas Balabanian, Karl Espéli, Marion Charron, Jean |
author_sort | Beuret, Laurent |
collection | PubMed |
description | Several studies have established the crucial role of the extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase pathway in hematopoietic cell proliferation and differentiation. MEK1 and MEK2 phosphorylate and activate ERK1 and ERK2. However, whether MEK1 and MEK2 differentially regulate these processes is unknown. To define the function of Mek genes in the activation of the ERK pathway during hematopoiesis, we generated a mutant mouse line carrying a hematopoietic-specific deletion of the Mek1 gene function in a Mek2 null background. Inactivation of both Mek1 and Mek2 genes resulted in death shortly after birth with a severe anemia revealing the essential role of the ERK pathway in erythropoiesis. Mek1 and Mek2 functional ablation also affected lymphopoiesis and myelopoiesis. In contrast, mice that retained one functional Mek1 (1Mek1) or Mek2 (1Mek2) allele in hematopoietic cells were viable and fertile. 1Mek1 and 1Mek2 mutants showed mild signs of anemia and splenomegaly, but the half-life of their red blood cells and the response to erythropoietic stress were not altered, suggesting a certain level of Mek redundancy for sustaining functional erythropoiesis. However, subtle differences in multipotent progenitor distribution in the bone marrow were observed in 1Mek1 mice, suggesting that the two Mek genes might differentially regulate early hematopoiesis. |
format | Online Article Text |
id | pubmed-8353236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83532362021-08-11 Mek1 and Mek2 Functional Redundancy in Erythropoiesis Beuret, Laurent Fortier-Beaulieu, Simon-Pierre Rondeau, Vincent Roy, Sophie Houde, Nicolas Balabanian, Karl Espéli, Marion Charron, Jean Front Cell Dev Biol Cell and Developmental Biology Several studies have established the crucial role of the extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase pathway in hematopoietic cell proliferation and differentiation. MEK1 and MEK2 phosphorylate and activate ERK1 and ERK2. However, whether MEK1 and MEK2 differentially regulate these processes is unknown. To define the function of Mek genes in the activation of the ERK pathway during hematopoiesis, we generated a mutant mouse line carrying a hematopoietic-specific deletion of the Mek1 gene function in a Mek2 null background. Inactivation of both Mek1 and Mek2 genes resulted in death shortly after birth with a severe anemia revealing the essential role of the ERK pathway in erythropoiesis. Mek1 and Mek2 functional ablation also affected lymphopoiesis and myelopoiesis. In contrast, mice that retained one functional Mek1 (1Mek1) or Mek2 (1Mek2) allele in hematopoietic cells were viable and fertile. 1Mek1 and 1Mek2 mutants showed mild signs of anemia and splenomegaly, but the half-life of their red blood cells and the response to erythropoietic stress were not altered, suggesting a certain level of Mek redundancy for sustaining functional erythropoiesis. However, subtle differences in multipotent progenitor distribution in the bone marrow were observed in 1Mek1 mice, suggesting that the two Mek genes might differentially regulate early hematopoiesis. Frontiers Media S.A. 2021-07-27 /pmc/articles/PMC8353236/ /pubmed/34386488 http://dx.doi.org/10.3389/fcell.2021.639022 Text en Copyright © 2021 Beuret, Fortier-Beaulieu, Rondeau, Roy, Houde, Balabanian, Espéli and Charron. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Beuret, Laurent Fortier-Beaulieu, Simon-Pierre Rondeau, Vincent Roy, Sophie Houde, Nicolas Balabanian, Karl Espéli, Marion Charron, Jean Mek1 and Mek2 Functional Redundancy in Erythropoiesis |
title | Mek1 and Mek2 Functional Redundancy in Erythropoiesis |
title_full | Mek1 and Mek2 Functional Redundancy in Erythropoiesis |
title_fullStr | Mek1 and Mek2 Functional Redundancy in Erythropoiesis |
title_full_unstemmed | Mek1 and Mek2 Functional Redundancy in Erythropoiesis |
title_short | Mek1 and Mek2 Functional Redundancy in Erythropoiesis |
title_sort | mek1 and mek2 functional redundancy in erythropoiesis |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353236/ https://www.ncbi.nlm.nih.gov/pubmed/34386488 http://dx.doi.org/10.3389/fcell.2021.639022 |
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