p38 Mitogen-activated Protein Kinase Pathway Promotes Skeletal Muscle Differentiation
Open accessAbstract
Differentiation of muscle cells is regulated by extracellular growth factors that transmit largely unknown signals into the cells. Some of these growth factors induce mitogen-activated protein kinase (MAPK) cascades within muscle cells. In this work we show that the kinase activity of p38 MAPK is induced early during terminal differentiation of L8 cells. Addition of a specific p38 inhibitor SB 203580 to myoblasts blocked their fusion to multinucleated myotubes and prevented the expression of MyoD and MEF2 family members and myosin light chain 2. The expression of MKK6, a direct activator of p38, or of p38 itself enhanced the activity of MyoD in converting 10T1/2 fibroblasts to muscle, whereas treatment with SB 203580 inhibited MyoD. Several lines of evidence suggesting that the involvement of p38 in MyoD activity is mediated via its co-activator MEF2C, a known substrate of p38, are presented. In these experiments we show that MEF2C protein and MEF2-binding sites are necessary for the p38 MAPK pathway to regulate the transcription of muscle creatine kinase reporter gene. Our results indicate that the p38 MAPK pathway promotes skeletal muscle differentiation at least in part via activation of MEF2C.
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MyoD activity is regulated by promyogenic signaling pathways including p38 MAPK and Akt.
“The activity of MyoD is regulated by promyogenic signaling pathways which include p38 mitogen-activated protein kinase (p38 MAPK) and Akt [5, 7, 8].”
From Apigenin Enhances Skeletal Muscle Hypertrophy and Myoblast Differentiation by Regulating Prmt7 (2017) · cites this paper as [7]
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- Authors
- Zetser, A., Gredinger, E., & Bengal, E.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Corresponding author
- Bengal, Eyal
- ORCID
- Bengal, Eyal
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 274
- Issue
- 8
- Pages
- 5193-5200
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2076276305
- Cited by
- 461
- References
- 45
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 10 · 2023: 2 · 2022: 12 · 2021: 12 · 2020: 10 · 2019: 13 · 2018: 15 · 2017: 15 · 2016: 23 · 2015: 13 · 2014: 13 · 2013: 20 · 2012: 16
- FWCI
- 11.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Rappaport Foundation
- Fondation pour la Recherche Médicale
- Israel Cancer Association
- Technion-Israel Institute of Technology
- 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 › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- p38 MAPK, skeletal muscle differentiation, myoblast fusion, MyoD, MEF2C, MEF2, MKK6, SB203580, muscle creatine kinase, transcriptional regulation, 10T1/2 fibroblasts, myotube formation
- MeSH terms
- Binding Sites, Cell Differentiation, Cell Line, Creatine Kinase, Enzyme Activation, Enzyme Inhibitors, Imidazoles, Phosphorylation, Pyridines, Transcription, Genetic, Calcium-Calmodulin-Dependent Protein Kinases, Myogenic Regulatory Factors, Muscle, Skeletal, Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, MAP Kinase Kinase 6, MEF2 Transcription Factors
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