Source:http://linkedlifedata.com/resource/pubmed/id/12209887
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2002-9-4
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| pubmed:abstractText |
Myostatin, a secreted growth factor, is a key negative regulator of skeletal muscle growth. To identify modifiers of Myostatin function, we screened for Myostatin interacting proteins. Using a yeast two-hybrid screen, we identified Titin-cap (T-cap) protein as interacting with Myostatin. T-cap is a sarcomeric protein that binds to the N-terminal domain of Titin and is a substrate of the titin kinase. Mammalian two-hybrid studies, in vitro binding assays and protein truncations in the yeast two-hybrid system verified the specific interaction between processed mature Myostatin and full-length T-cap. Analysis of protein-protein interaction using surface plasmon resonance (Biacore, Uppsala, Sweden) kinetics revealed a high affinity between Myostatin and T-cap with a KD of 40 nM. When T-cap was stably overexpressed in C(2)C(12) myoblasts, the rate of cell proliferation was significantly increased. Western analyses showed that production and processing of Myostatin were not altered in cells overexpressing T-cap, but an increase in the retention of mature Myostatin indicated that T-cap may block Myostatin secretion. Bioassay for Myostatin confirmed that conditioned media from myoblasts overexpressing T-cap contained lower levels of Myostatin. Given that Myostatin negatively regulates myoblast proliferation, the increase in proliferation observed in myoblasts overexpressing T-cap could thus be due to reduced Myostatin secretion. These results suggest that T-cap, by interacting with Myostatin, controls Myostatin secretion in myogenic precursor cells without affecting the processing step of precursor Myostatin.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned,
http://linkedlifedata.com/resource/pubmed/chemical/Mstn protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myostatin,
http://linkedlifedata.com/resource/pubmed/chemical/Tcap protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-9541
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2002 Wiley-Liss, Inc.
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| pubmed:issnType |
Print
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| pubmed:volume |
193
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
120-31
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:12209887-Animals,
pubmed-meshheading:12209887-Blotting, Western,
pubmed-meshheading:12209887-CHO Cells,
pubmed-meshheading:12209887-Cell Division,
pubmed-meshheading:12209887-Cell Line,
pubmed-meshheading:12209887-Cricetinae,
pubmed-meshheading:12209887-Culture Media, Conditioned,
pubmed-meshheading:12209887-Genes, Reporter,
pubmed-meshheading:12209887-Kinetics,
pubmed-meshheading:12209887-Mice,
pubmed-meshheading:12209887-Muscle, Skeletal,
pubmed-meshheading:12209887-Muscle Proteins,
pubmed-meshheading:12209887-Myostatin,
pubmed-meshheading:12209887-Protein Binding,
pubmed-meshheading:12209887-Saccharomyces cerevisiae,
pubmed-meshheading:12209887-Sequence Deletion,
pubmed-meshheading:12209887-Surface Plasmon Resonance,
pubmed-meshheading:12209887-Transfection,
pubmed-meshheading:12209887-Transforming Growth Factor beta,
pubmed-meshheading:12209887-Two-Hybrid System Techniques
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| pubmed:year |
2002
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| pubmed:articleTitle |
Titin-cap associates with, and regulates secretion of, Myostatin.
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| pubmed:affiliation |
Animal Genomics, AgResearch, East Street, Hamilton, New Zealand.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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