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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...

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Autores principales: Beuret, Laurent, Fortier-Beaulieu, Simon-Pierre, Rondeau, Vincent, Roy, Sophie, Houde, Nicolas, Balabanian, Karl, Espéli, Marion, Charron, Jean
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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.
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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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