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Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein Kinases
Abstract
The signal transduction pathway or pathways linking extracellular signals to myogenesis are poorly defined. Upon mitogen withdrawal from C2C12 myoblasts, the mitogen-activated protein kinase (MAPK) p42Erk2 is inactivated concomitant with up-regulation of muscle-specific genes. Overexpression of MAPK phosphatase-1 (MKP-1) inhibited p42Erk2 activity and was sufficient to relieve the inhibitory effects of mitogens on muscle-specific gene expression. Later during myogenesis, endogenous expression of MKP-1 decreased. MKP-1 overexpression during differentiation prevented myotube formation despite appropriate expression of myosin heavy chain. This indicates that muscle-specific gene expression is necessary but not sufficient to commit differentiated myocytes to myotubes and suggests a function for the MAPKs during the early and late stages of skeletal muscle differentiation.
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“The MAPK cascade(s), particularly the extracellular signal-regulated kinases (ERK) 1 and 2 (ERK1/2), play a duel role in myogenesis [125,126].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [125]
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Differentiation Stage-Specific Inhibition of the Raf-MEK-ERK Pathway by Akt
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The molecular regulation of myogenesis
Sabourin, L. A., & Rudnicki, M. A. (2000) · Clinical Genetics · doi:10.1034/j.1399-0004.2000.570103.x · Cited by 720
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Metadata
- Authors
- Bennett, A. M., & Tonks, N. K.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Tonks, Nicholas K.
- Venue
- Science
- Published
- 1997-11-14
- Volume
- 278
- Issue
- 5341
- Pages
- 1288-1291
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1975358464
- Cited by
- 359
- References
- 28
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 5 · 2022: 4 · 2021: 14 · 2020: 10 · 2019: 5 · 2018: 12 · 2017: 9 · 2016: 9 · 2015: 7 · 2014: 13 · 2013: 12 · 2012: 11
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- skeletal muscle differentiation, myogenesis, mitogen-activated protein kinase, MAPK phosphatase-1, MKP-1, C2C12 myoblasts, muscle-specific gene expression, myotube formation, signal transduction, myosin heavy chain
- MeSH terms
- Animals, Cell Differentiation, Cell Division, Cell Line, Cloning, Molecular, Culture Media, Mitogens, Muscle Proteins, Phosphoprotein Phosphatases, Phosphorylation, Recombinant Fusion Proteins, Tetracycline, Transcription, Genetic, Signal Transduction, Protein Tyrosine Phosphatases, Calcium-Calmodulin-Dependent Protein Kinases, Immediate-Early Proteins, Muscle, Skeletal, Gene Expression Regulation, Developmental, Cell Cycle Proteins, Cyclin D1, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, Mice, Dual Specificity Phosphatase 1, Protein Phosphatase 1
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