Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein Kinases

• Published in: Science (American Association for the Advancement of Science) 1997-11, Vol.278 (5341), p.1288-1291
• Main Authors: Bennett, Anton M., Tonks, Nicholas K.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Biological and medical sciences; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cell cycle; Cell Cycle Proteins; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell Division; Cell Line; Cell physiology; Cellular signal transduction; Cloning, Molecular; Culture Media; Cyclin D1 - genetics; Cyclins; Dual Specificity Phosphatase 1; Fundamental and applied biological sciences. Psychology; Gene expression regulation; Gene Expression Regulation, Developmental; Genes; Genetically modified organisms; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Individualized Instruction; Inhibition; JNK Mitogen-Activated Protein Kinases; Mice; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinases; Mitogens; Mitogens - pharmacology; Molecular and cellular biology; Muscle cells; Muscle development; Muscle fibers; Muscle Proteins - genetics; Muscle, Skeletal - cytology; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Muscular system; Myoblasts; Phosphoprotein Phosphatases; Phosphorylation; Protein Phosphatase 1; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - metabolism; Proteins; Recombinant Fusion Proteins - metabolism; Signal Transduction; Skeletal muscle; Skeletal system; Tetracycline - pharmacology; Transcription, Genetic
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.278.5341.1288

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.