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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 25
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pubmed:dateCreated |
2004-11-26
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pubmed:abstractText |
Extracellular signaling pathways regulating myoblast differentiation and cell-cycle withdrawal are not completely understood. Stem cell antigen-1 (Sca-1/Ly-6A/E) is a glycosylphosphatidylinositol-anchored membrane protein known for its role in T-cell activation, and recently described as a marker for regeneration-competent myoblasts. We previously determined that expression of Sca-1/Ly-6A is transiently upregulated during myocyte cell-cycle withdrawal; however, a specific function for Sca-1 in myogenesis has not been described. Here, we show that Sca-1 expression on the surface of a subpopulation of differentiating C2C12 myoblasts is maximal at the time of cell-cycle withdrawal, and that blocking Sca-1 with monoclonal antibodies or downregulating Sca-1 expression by antisense both promotes proliferation and inhibits myotube formation. Downregulating Sca-1 expression derepresses Fyn at the time of myoblast cell-cycle withdrawal, and dominant-negative and constitutively active Fyn mutants rescue and recapitulate the Sca-1 antisense phenotype, respectively. This suggests a Fyn-mediated mechanism for Sca-1 action. Thus, we demonstrate an unprecedented role for Sca-1 in early myogenesis in C2C12 cells, and propose a novel pathway from the myoblast cell surface to intracellular signaling networks controlling proliferation versus differentiation in mammalian muscle. These findings suggest that, beyond its role as a marker for muscle progenitors, Sca-1 may be an important therapeutic target for promoting muscle regeneration.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Ly,
http://linkedlifedata.com/resource/pubmed/chemical/Bromodeoxyuridine,
http://linkedlifedata.com/resource/pubmed/chemical/Coloring Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Fyn protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glycosylphosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Ly6a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fyn,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9533
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6185-95
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15546912-Animals,
pubmed-meshheading:15546912-Antibodies, Monoclonal,
pubmed-meshheading:15546912-Antigens, Differentiation, T-Lymphocyte,
pubmed-meshheading:15546912-Antigens, Ly,
pubmed-meshheading:15546912-Bromodeoxyuridine,
pubmed-meshheading:15546912-Cell Cycle,
pubmed-meshheading:15546912-Cell Differentiation,
pubmed-meshheading:15546912-Cell Line,
pubmed-meshheading:15546912-Cell Membrane,
pubmed-meshheading:15546912-Cell Proliferation,
pubmed-meshheading:15546912-Coloring Agents,
pubmed-meshheading:15546912-Dose-Response Relationship, Drug,
pubmed-meshheading:15546912-Down-Regulation,
pubmed-meshheading:15546912-Flow Cytometry,
pubmed-meshheading:15546912-Genes, Dominant,
pubmed-meshheading:15546912-Genetic Vectors,
pubmed-meshheading:15546912-Glycosylphosphatidylinositols,
pubmed-meshheading:15546912-Immunoblotting,
pubmed-meshheading:15546912-Membrane Proteins,
pubmed-meshheading:15546912-Mice,
pubmed-meshheading:15546912-Mice, Inbred C57BL,
pubmed-meshheading:15546912-Muscle, Skeletal,
pubmed-meshheading:15546912-Muscle Cells,
pubmed-meshheading:15546912-Muscles,
pubmed-meshheading:15546912-Mutation,
pubmed-meshheading:15546912-Myoblasts,
pubmed-meshheading:15546912-Oligonucleotides, Antisense,
pubmed-meshheading:15546912-Phenotype,
pubmed-meshheading:15546912-Proto-Oncogene Proteins,
pubmed-meshheading:15546912-Proto-Oncogene Proteins c-fyn,
pubmed-meshheading:15546912-Regeneration,
pubmed-meshheading:15546912-Signal Transduction,
pubmed-meshheading:15546912-Stem Cells,
pubmed-meshheading:15546912-Time Factors,
pubmed-meshheading:15546912-Transfection,
pubmed-meshheading:15546912-Up-Regulation,
pubmed-meshheading:15546912-src-Family Kinases
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pubmed:year |
2004
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pubmed:articleTitle |
Stem cell antigen-1 is necessary for cell-cycle withdrawal and myoblast differentiation in C2C12 cells.
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pubmed:affiliation |
Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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