title: SOCS-3 induces myoblast differentiation.
abstract: Myoblast differentiation is characterized by a sequence of events that includes an increase in insulin-like growth factor (IGF)-I and contractile gene expression. The increase in IGF-I expression activates cell signaling mechanisms that participate in the differentiation process. One potential contributor is the SOCS-3 (suppressor of cytokine signaling-3) gene, which regulates signaling mechanisms and may be sensitive to changes in IGF-I concentrations. For the first time, the role of SOCS-3 is investigated in myoblast differentiation. SOCS-3 mRNA levels and SOCS-3 transcriptional activity increase during myoblast differentiation. SOCS-3 gene expression is induced, at least in part, by activation of the IGF-I receptor during myoblast differentiation. Overexpression of SOCS-3 cDNA significantly increased transcriptional activation of the 2.0-kb skeletal alpha-actin promoter in differentiating C2C12 myoblasts. In addition, overexpression of SOCS-3 specifically increased serum response factor-driven transcriptional activity but had no effect on nuclear-factor of activated T cell-driven transcriptional activity. SOCS-3 overexpression induced skeletal alpha-actin transcription in a myoblast cell line that cannot respond to endogenous IGF-I, indicating that SOCS-3 can contribute to the myoblast differentiation process in the absence of IGF-I. These data suggest that IGF-I induces myoblast differentiation, in part, by increasing SOCS-3 expression.
authors.affiliation: Exercise Biology Program, Division of Biological Sciences, and the Department of Physiology and Membrane Biology, School of Medicine, University of California-Davis, California 95616, USA. eespangenburg@ucdavis.edu
authors.forename: Espen E
authors.initials: EE
authors.lastname: Spangenburg
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000166:cytology; D032446:Myoblasts / Q000166:cytology*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000199:Actins; D018076:DNA, Complementary; D008024:Ligands; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I; D008156:Luciferases; D017526:Receptor, IGF Type 1