Abstract
Extracellular signals often result in simultaneous activation of both the Raf-MEK-ERK and PI3K-Akt pathways (where ERK is extracellular-regulated kinase, MEK is mitogen-activated protein kinase or ERK kinase, and PI3K is phosphatidylinositol 3-kinase). However, these two signaling pathways were shown to exert opposing effects on muscle cell hypertrophy. Furthermore, the PI3K-Akt pathway was shown to inhibit the Raf-MEK-ERK pathway; this cross-regulation depended on the differentiation state of the cell: Akt activation inhibited the Raf-MEK-ERK pathway in differentiated myotubes, but not in their myoblast precursors. The stage-specific inhibitory action of Akt correlated with its stage-specific ability to form a complex with Raf, suggesting the existence of differentially expressed mediators of an inhibitory Akt-Raf complex.
MeSH terms
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Animals
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Cell Differentiation
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Cell Line
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Insulin-Like Growth Factor I / pharmacology
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MAP Kinase Signaling System / drug effects
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Mice
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Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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Mitogen-Activated Protein Kinases / metabolism
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Muscle, Skeletal / cytology*
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Muscle, Skeletal / metabolism*
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Myogenin / genetics
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Phenotype
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-raf / antagonists & inhibitors*
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Proto-Oncogene Proteins c-raf / metabolism
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Signal Transduction
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Transfection
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Transgenes
Substances
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Enzyme Inhibitors
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Flavonoids
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Myog protein, mouse
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Myogenin
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Proto-Oncogene Proteins
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Insulin-Like Growth Factor I
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-raf
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Mitogen-Activated Protein Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one