Selective Control of Skeletal Muscle Differentiation by Akt1

The phosphatidylinositol 3-kinase-Akt pathway plays a central role in growth, development, and metabolism in both normal and neoplastic cells. In skeletal muscle, Akt has been implicated in regulating regeneration and hypertrophy and in counteracting atrophy. Here we provide evidence that Akt1 and n...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-02, Vol.282 (8), p.5106-5110
Main Authors: Wilson, Elizabeth M., Rotwein, Peter
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - physiology
Cell Line
Mice
Muscle Development - physiology
Muscle, Skeletal - enzymology
Myoblasts, Skeletal - enzymology
MyoD Protein - metabolism
Neoplasms, Muscle Tissue - genetics
Neoplasms, Muscle Tissue - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Protein Isoforms - genetics
Protein Isoforms - metabolism
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
Signal Transduction - physiology
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Summary:The phosphatidylinositol 3-kinase-Akt pathway plays a central role in growth, development, and metabolism in both normal and neoplastic cells. In skeletal muscle, Akt has been implicated in regulating regeneration and hypertrophy and in counteracting atrophy. Here we provide evidence that Akt1 and not Akt2 is essential for muscle differentiation. Using a robust model of MyoD-mediated muscle development, in which dominant-negative Akt blocked differentiation, we show that targeted loss of Akt1 was equally inhibitory. Selective elimination of Akt1 had no effect on myoblast viability or proliferation but prevented differentiation by impairing the transcriptional actions of MyoD. In contrast, knockdown of Akt2 had no effect on myoblast survival or differentiation and minimally inhibited MyoD-regulated transcription. Our results define isoform-specific Akt-regulated signaling pathways in muscle cells that act through Akt1 to sustain muscle gene activation and promote differentiation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C600315200