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Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin.
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MedLine Citation:
PMID:  2139036     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Medium conditioned by Chinese hamster ovary (CHO) cells transfected with the simian pre-pro-TGF beta 1 cDNA contains high levels of latent TGF beta 1. The amino-terminal region of the TGF beta 1 precursor is secreted and can be detected in the conditioned medium by immunoblotting using peptide antibodies specific for amino-terminal peptides. Chemical cross-linking of CHO-conditioned medium using bis-(sulfosuccinimidyl)-suberate (BS3) followed by immunoblot analyses indicates that latent recombinant TGF beta 1 contains both the cleaved amino-terminal glycopeptide and mature TGF beta 1 polypeptide in a noncovalent association and that this association confers latency. The data presented here do not support the involvement of a unique TGF beta binding protein(s) in latent recombinant TGF beta 1. Plasmin treatment of CHO-conditioned medium resulted in the appearance of TGF beta competing activity. In addition, immunoblot analysis of plasmin-treated CHO-conditioned medium indicates that the amino-terminal glycopeptide is partially degraded and that mature TGF beta 1 is released. Thus, activation of latent TGF beta 1 may occur by proteolytic nicking within the amino-terminal glycopeptide thereby causing a disruption of tertiary structure and noncovalent bonds, which results in the release of active, mature TGF beta 1. Acid activation of latent TGF beta, in comparison, appears to be due to dissociation of the amino-terminal glycopeptide from the mature polypeptide.
Authors:
R M Lyons; L E Gentry; A F Purchio; H L Moses
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of cell biology     Volume:  110     ISSN:  0021-9525     ISO Abbreviation:  J. Cell Biol.     Publication Date:  1990 Apr 
Date Detail:
Created Date:  1990-05-11     Completed Date:  1990-05-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0375356     Medline TA:  J Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1361-7     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Vanderbilt School of Medicine, Nashville, Tennessee 37232.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Fibrinolysin / metabolism*
Haplorhini
Immunoblotting
Models, Structural
Molecular Weight
Protein Precursors*
Proteins / genetics
Radioligand Assay
Recombinant Proteins / metabolism
Transfection
Transforming Growth Factor beta*
Transforming Growth Factors / genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
CA42572/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Protein Precursors; 0/Proteins; 0/Recombinant Proteins; 0/Transforming Growth Factor beta; 76057-06-2/Transforming Growth Factors; EC 3.4.21.7/Fibrinolysin
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): J Cell Biol
ISSN: 0021-9525
ISSN: 1540-8140
Publisher: The Rockefeller University Press
Article Information
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Print publication date: Day: 1 Month: 4 Year: 1990
Volume: 110 Issue: 4
First Page: 1361 Last Page: 1367
ID: 2116088
Publisher Id: 90216872
PubMed Id: 2139036

Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin


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