title: Selective control of skeletal muscle differentiation by Akt1.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Wilson
authors.forename: Peter
authors.initials: P
authors.lastname: Rotwein
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D051379:Mice; D024510:Muscle Development / Q000502:physiology; D018482:Muscle, Skeletal / Q000201:enzymology*; D017570:MyoD Protein / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000201:enzymology*; D009379:Neoplasms, Muscle Tissue / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017570:MyoD Protein; D020033:Protein Isoforms; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt