Cited by 137Muscle Physiology and DisordersDevelopmental Biology and Gene RegulationMuscle metabolism and nutrition

ERK2 is required for efficient terminal differentiation of skeletal myoblasts

Li, Ju, Johnson, Sally E.·2006·Biochemical and Biophysical Research Communications

Abstract

Terminal differentiation of skeletal myoblasts involves alignment of the mononucleated cells, fusion into multinucleated syncitia, and transcription of muscle-specific genes. Myogenesis in vivo is regulated partially by IGF-I initiated signaling that results in activation of an intracellular phosphatidylinositol 3 kinase (PI3K) signaling cascade. Downstream signaling through the Raf/MEK/ERK axis, a pathway initiated by IGF-I, also is implicated in the regulation of muscle formation. The involvement of ERK1 and ERK2 during myogenesis was examined in C2C12 myoblasts. C2C12 myoblasts stably expressing a small interfering RNA (siRNA) directed against ERK1 or ERK2 were created. Both of the kinases were reduced to trace levels as measured by Western for total ERK and retained the capacity to become phosphorylated. C2C12siERK2 knockdown myoblasts failed to fuse into multinucleated myofibers. By contrast, cells expressing a scrambled siRNA or ERK1 siRNA fused into large multinucleated structures. The block to muscle formation did not involve continued cell cycle progression or apoptosis. C2C12siERK1 myoblasts expressed an increased amount of ERK2 protein and formed larger myofibers in response to IGF-I treatment. Interestingly, IGF-I treatment of C2C12 ERK2 knockdown myoblasts did not reinstate the myogenic program arguing that ERK2 is required for differentiation. These results provide evidence for ERK2 as a positive regulator of myogenesis and suggest that ERK1 is dispensable for myoblast proliferation and differentiation.

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Crossref · 10.1016/j.bbrc.2006.05.051

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  • During late stages of differentiation, ERK1/2 becomes phosphorylated, promoting fusion and formation of myotubes.

    “In contrast to this inhibitory effect during the early stages of differentiation ERK1/2 becomes phosphorylated during the late stages of differentiation promoting the fusion and formation of myotubes [129,130].”

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Authors
Li, J., & Johnson, S. E.
Affiliations
University of Florida (US)
Corresponding author
Johnson, Sally E.
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2006-07
Volume
345
Issue
4
Pages
1425-1433
ISSN
0006-291X (ISSN-L)
OpenAlex
W2011006146
Cited by
137
References
227
Citations by year
2025: 3 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 9 · 2016: 8 · 2015: 10 · 2014: 7 · 2013: 15 · 2012: 6
FWCI
2.59
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
Funders
U.S. Public Health Service (R01-AR048830)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
ERK2, ERK1, myogenesis, skeletal myoblasts, terminal differentiation, IGF-1 signaling, Raf/MEK/ERK pathway, PI3K signaling, C2C12 myoblasts, siRNA knockdown
MeSH terms
Cell Differentiation, Cell Line, Insulin-Like Growth Factor I, Myofibrils, Transfection, Blotting, Western, Signal Transduction, Fibroblast Growth Factor 2, Myogenin, Mitogen-Activated Protein Kinase 1, Myoblasts, Skeletal, RNA, Small Interfering, Mitogen-Activated Protein Kinase 3, Cell Proliferation

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