Source:http://linkedlifedata.com/resource/pubmed/id/10766842
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
16
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pubmed:dateCreated |
2000-5-10
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pubmed:abstractText |
Thrombopoietin (TPO) is a cytokine that primarily stimulates megakaryocytopoiesis and thrombopoiesis. TPO has a unique C-terminal tail peptide of about 160 amino acids that consists mostly of hydrophilic residues and contains six N-linked sugar chains. In order to investigate the biological function of the C-terminal domain, two series of mutations were performed. One is systematic truncation from the C terminus. Another is elimination of N-glycosylation sites in the C-terminal domain by Asn to Gln mutations. After the mutant proteins were expressed by mammalian cells, it was found that the elimination of the N-linked sugar sites did not affect the biological activity, whereas truncation of the C-terminal domain resulted in elevation of in vitro activity up to 4-fold. The C-terminal peptide itself was found to inhibit the in vitro activity. Moreover, both the C-terminal truncation and the elimination of the N-glycosylation sites decreased the secretion level progressively down to (1)/(10) that of wild type, and the amount of the mutant left in the cell increased. The N-glycosylation in the C-terminal region was found to be important for secretion of TPO. Among six N-glycosylation sites in the C-terminal region, two locations, Asn-213 and Asn-234, were found to be critical for secretion, and two other locations, Asn-319 and Asn-327, did not affect the secretion.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12090-4
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:10766842-Animals,
pubmed-meshheading:10766842-Asparagine,
pubmed-meshheading:10766842-Blotting, Western,
pubmed-meshheading:10766842-COS Cells,
pubmed-meshheading:10766842-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:10766842-Glutamine,
pubmed-meshheading:10766842-Glycosylation,
pubmed-meshheading:10766842-Humans,
pubmed-meshheading:10766842-Mutagenesis, Site-Directed,
pubmed-meshheading:10766842-Recombinant Proteins,
pubmed-meshheading:10766842-Structure-Activity Relationship,
pubmed-meshheading:10766842-Thrombopoietin
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pubmed:year |
2000
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pubmed:articleTitle |
Functional analysis of the C-terminal region of recombinant human thrombopoietin. C-terminal region of thrombopoietin is a "shuttle" peptide to help secretion.
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pubmed:affiliation |
Central Laboratories for Key Technology, Kirin Brewery Co., Ltd., 1-13-5 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236, Japan.
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pubmed:publicationType |
Journal Article
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