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p38 and extracellular signal-regulated kinases regulate the myogenic program at multiple steps
Z Wu1, P J Woodring, K S Bhakta
1Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, California 92093-0322, USA.
Molecular and Cellular Biology
|May 11, 2000
Summary
Mitogen-activated protein kinases (MAPKs) regulate muscle growth. The study shows p38 activation is crucial for muscle differentiation, while extracellular signal-regulated kinase (ERK) has a dual role in myoblasts and myotubes.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Extracellular signals regulate muscle differentiation via mitogen-activated protein kinases (MAPKs).
- p38 and extracellular signal-regulated kinase (ERK) activities change significantly during muscle differentiation.
Purpose of the Study:
- To investigate the roles of p38 and ERK in muscle differentiation.
- To elucidate the mechanisms by which these MAPKs influence myogenic transcription factors like MyoD and MEF2.
Main Methods:
- Utilized myogenic cell lines and human primary myocytes.
- Employed genetic manipulation (p38alpha(-/-) embryos) and pharmacological inhibition/activation of MAPKs.
- Assessed gene expression, protein phosphorylation, and transcriptional activity of myogenic factors.
Main Results:
- p38 activation is rapid, sustained, and essential for myogenesis, independent of IGF-1.
- p38 directly activates MyoD and enhances MEF2A/MEF2C transcriptional activity.
- ERK exhibits a biphasic activation; inhibitory in myoblasts but promotes transcription and hypertrophic growth in myotubes.
Conclusions:
- p38 acts as a key activator of the myogenic program by modulating MyoD and MEF2.
- ERK plays distinct roles in different stages of muscle development, inhibiting early differentiation but promoting later growth.
- Targeting p38 signaling holds potential for therapeutic interventions in muscle-related disorders.
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