Cited by 359Muscle Physiology and DisordersProtein Tyrosine PhosphatasesDevelopmental Biology and Gene Regulation

Regulation of distinct stages of skeletal muscle differentiation by mitogen-activated protein kinases

Bennett, Anton M., Tonks, Nicholas K.·1997·Science

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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Crossref · 10.1126/science.278.5341.1288

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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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