Regulation of distinct stages of skeletal muscle differentiation by mitogen-activated protein kinases.
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.
Bennett
A M
AM
Cold Spring Harbor Laboratory, Demerec Building, 1 Bungtown Road, Post Office Box 100, Cold Spring Harbor, NY 11724, USA.
Tonks
N K
NK
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D003001:Cloning, Molecular; D003470:Culture Media; D019938:Cyclin D1 / Q000235:genetics; D054638:Dual Specificity Phosphatase 1; D018507:Gene Expression Regulation, Developmental; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases; D008934:Mitogens / Q000494:pharmacology; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013752:Tetracycline / Q000494:pharmacology; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D003470:Culture Media; D017874:Immediate-Early Proteins; D008934:Mitogens; D009124:Muscle Proteins; D011993:Recombinant Fusion Proteins; D019938:Cyclin D1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D017027:Protein Tyrosine Phosphatases; D013752:Tetracycline