Source:http://linkedlifedata.com/resource/pubmed/id/15606553
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2004-12-20
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pubmed:abstractText |
This study investigated the functional impact of O-linked glycosylation of von Willebrand Factor (VWF) A1 domains on the interaction with platelet receptors. Native or mutant VWF-A1-domains were transiently overexpressed on COS-7 cells as membrane glycosylphosphatidylinositol (GPI)-anchored FLAG-tagged fusion proteins. Cytofluometric analysis assured comparable levels of A1-domain expression among native and mutant homologues as well as for different culture conditions. Expressing native VWF-A1-domains under O-linked glycosylation blocking conditions increased the platelet aggregatory responses observed for fully glycosylated forms. Utilizing a neuronal network for prediction of O-linked glycosylation of mammalian proteins, threonine (T) and serine (S) residues located in the VWF-A1-loop flanking regions - not in the loop itself - were determined to be glycosylated n-terminal at amino acids T485, S490, T492 and T493 and c-terminal at T705. Simultaneous selective charge-to-alanine mutation of S490, T492 and T493 led to gain in aggregatory responses. When compared with native forms, equivalent alterations of T485 did not dictate functional differences. Any alanine-substitution for T705 revealed a substantial loss in aggregatory effects - possibly as a result of structural desintegration of the VWF-A1-binding site for glycoprotein (GP) Ib. These data suggest specific O-linked glycosylation of the amino-terminal VWF-A1-loop-flanking region to have a negative regulatory impact on the A1-domain affinity of non-activated human VWF for human platelet-GPIb.
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pubmed:grant | |
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 |
Jan
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pubmed:issn |
0007-1048
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
128
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
82-90
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15606553-Amino Acids,
pubmed-meshheading:15606553-Animals,
pubmed-meshheading:15606553-Blood Platelets,
pubmed-meshheading:15606553-COS Cells,
pubmed-meshheading:15606553-Gene Expression,
pubmed-meshheading:15606553-Glycosylation,
pubmed-meshheading:15606553-Humans,
pubmed-meshheading:15606553-Mutagenesis, Site-Directed,
pubmed-meshheading:15606553-Platelet Aggregation,
pubmed-meshheading:15606553-Platelet Glycoprotein GPIb-IX Complex,
pubmed-meshheading:15606553-Protein Structure, Tertiary,
pubmed-meshheading:15606553-von Willebrand Factor
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pubmed:year |
2005
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pubmed:articleTitle |
Impact of O-linked glycosylation of the VWF-A1-domain flanking regions on platelet interaction.
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pubmed:affiliation |
Clinic for General and Visceral Surgery, Heinrich Heine University Duesseldorf, Germany. jan.schulteamesch@uni-duesseldorf.de
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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