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EphrinA/EphA signal facilitates insulin-like growth factor-I–induced myogenic differentiation through suppression of the Ras/extracellular signal–regulated kinase 1/2 cascade in myoblast cell lines

Insulin-like growth factor-I (IGF-I) activates not only the phosphatidylinositol 3-kinase (PI3K)–AKT cascade that is essential for myogenic differentiation but also the extracellular signal–regulated kinase (ERK) 1/2 cascade that inhibits myogenesis. We hypothesized that there must be a signal that...

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Autores principales: Minami, Masayoshi, Koyama, Tatsuya, Wakayama, Yuki, Fukuhara, Shigetomo, Mochizuki, Naoki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172274/
https://www.ncbi.nlm.nih.gov/pubmed/21795402
http://dx.doi.org/10.1091/mbc.E11-03-0183
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author Minami, Masayoshi
Koyama, Tatsuya
Wakayama, Yuki
Fukuhara, Shigetomo
Mochizuki, Naoki
author_facet Minami, Masayoshi
Koyama, Tatsuya
Wakayama, Yuki
Fukuhara, Shigetomo
Mochizuki, Naoki
author_sort Minami, Masayoshi
collection PubMed
description Insulin-like growth factor-I (IGF-I) activates not only the phosphatidylinositol 3-kinase (PI3K)–AKT cascade that is essential for myogenic differentiation but also the extracellular signal–regulated kinase (ERK) 1/2 cascade that inhibits myogenesis. We hypothesized that there must be a signal that inhibits ERK1/2 upon cell–cell contact required for skeletal myogenesis. Cell–cell contact–induced engagement of ephrin ligands and Eph receptors leads to downregulation of the Ras-ERK1/2 pathway through p120 Ras GTPase-activating protein (p120RasGAP). We therefore investigated the significance of the ephrin/Eph signal in IGF-I–induced myogenesis. EphrinA1-Fc suppressed IGF-I–induced activation of Ras and ERK1/2, but not that of AKT, in C2C12 myoblasts, whereas ephrinB1-Fc affected neither ERK1/2 nor AKT activated by IGF-I. IGF-I–dependent myogenic differentiation of C2C12 myoblasts was potentiated by ephrinA1-Fc. In p120RasGAP-depleted cells, ephrinA1-Fc failed to suppress the Ras-ERK1/2 cascade by IGF-I and to promote IGF-I–mediated myogenesis. EphrinA1-Fc did not promote IGF-I–dependent myogenesis when the ERK1/2 was constitutively activated. Furthermore, a dominant-negative EphA receptor blunted IGF-I–induced myogenesis in C2C12 and L6 myoblasts. However, the inhibition of IGF-I–mediated myogenesis by down-regulation of ephrinA/EphA signal was canceled by inactivation of the ERK1/2 pathway. Collectively, these findings demonstrate that the ephrinA/EphA signal facilitates IGF-I–induced myogenesis by suppressing the Ras-ERK1/2 cascade through p120RasGAP in myoblast cell lines.
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spelling pubmed-31722742011-11-30 EphrinA/EphA signal facilitates insulin-like growth factor-I–induced myogenic differentiation through suppression of the Ras/extracellular signal–regulated kinase 1/2 cascade in myoblast cell lines Minami, Masayoshi Koyama, Tatsuya Wakayama, Yuki Fukuhara, Shigetomo Mochizuki, Naoki Mol Biol Cell Articles Insulin-like growth factor-I (IGF-I) activates not only the phosphatidylinositol 3-kinase (PI3K)–AKT cascade that is essential for myogenic differentiation but also the extracellular signal–regulated kinase (ERK) 1/2 cascade that inhibits myogenesis. We hypothesized that there must be a signal that inhibits ERK1/2 upon cell–cell contact required for skeletal myogenesis. Cell–cell contact–induced engagement of ephrin ligands and Eph receptors leads to downregulation of the Ras-ERK1/2 pathway through p120 Ras GTPase-activating protein (p120RasGAP). We therefore investigated the significance of the ephrin/Eph signal in IGF-I–induced myogenesis. EphrinA1-Fc suppressed IGF-I–induced activation of Ras and ERK1/2, but not that of AKT, in C2C12 myoblasts, whereas ephrinB1-Fc affected neither ERK1/2 nor AKT activated by IGF-I. IGF-I–dependent myogenic differentiation of C2C12 myoblasts was potentiated by ephrinA1-Fc. In p120RasGAP-depleted cells, ephrinA1-Fc failed to suppress the Ras-ERK1/2 cascade by IGF-I and to promote IGF-I–mediated myogenesis. EphrinA1-Fc did not promote IGF-I–dependent myogenesis when the ERK1/2 was constitutively activated. Furthermore, a dominant-negative EphA receptor blunted IGF-I–induced myogenesis in C2C12 and L6 myoblasts. However, the inhibition of IGF-I–mediated myogenesis by down-regulation of ephrinA/EphA signal was canceled by inactivation of the ERK1/2 pathway. Collectively, these findings demonstrate that the ephrinA/EphA signal facilitates IGF-I–induced myogenesis by suppressing the Ras-ERK1/2 cascade through p120RasGAP in myoblast cell lines. The American Society for Cell Biology 2011-09-15 /pmc/articles/PMC3172274/ /pubmed/21795402 http://dx.doi.org/10.1091/mbc.E11-03-0183 Text en © 2011 Minami et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Minami, Masayoshi
Koyama, Tatsuya
Wakayama, Yuki
Fukuhara, Shigetomo
Mochizuki, Naoki
EphrinA/EphA signal facilitates insulin-like growth factor-I–induced myogenic differentiation through suppression of the Ras/extracellular signal–regulated kinase 1/2 cascade in myoblast cell lines
title EphrinA/EphA signal facilitates insulin-like growth factor-I–induced myogenic differentiation through suppression of the Ras/extracellular signal–regulated kinase 1/2 cascade in myoblast cell lines
title_full EphrinA/EphA signal facilitates insulin-like growth factor-I–induced myogenic differentiation through suppression of the Ras/extracellular signal–regulated kinase 1/2 cascade in myoblast cell lines
title_fullStr EphrinA/EphA signal facilitates insulin-like growth factor-I–induced myogenic differentiation through suppression of the Ras/extracellular signal–regulated kinase 1/2 cascade in myoblast cell lines
title_full_unstemmed EphrinA/EphA signal facilitates insulin-like growth factor-I–induced myogenic differentiation through suppression of the Ras/extracellular signal–regulated kinase 1/2 cascade in myoblast cell lines
title_short EphrinA/EphA signal facilitates insulin-like growth factor-I–induced myogenic differentiation through suppression of the Ras/extracellular signal–regulated kinase 1/2 cascade in myoblast cell lines
title_sort ephrina/epha signal facilitates insulin-like growth factor-i–induced myogenic differentiation through suppression of the ras/extracellular signal–regulated kinase 1/2 cascade in myoblast cell lines
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172274/
https://www.ncbi.nlm.nih.gov/pubmed/21795402
http://dx.doi.org/10.1091/mbc.E11-03-0183
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