Source:http://linkedlifedata.com/resource/pubmed/id/20466649
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rdf:type | |
lifeskim:mentions |
umls-concept:C0014139,
umls-concept:C0086418,
umls-concept:C0178539,
umls-concept:C0208973,
umls-concept:C0242372,
umls-concept:C0686904,
umls-concept:C0813622,
umls-concept:C1148609,
umls-concept:C1425660,
umls-concept:C1514562,
umls-concept:C1517892,
umls-concept:C1704666,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C1998793
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pubmed:issue |
8
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pubmed:dateCreated |
2010-7-5
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pubmed:abstractText |
The hyaluronic acid receptor for endocytosis (HARE)/Stabilin-2 is the primary systemic scavenger receptor for 13 ligands including hyaluronan (HA), heparin and chondroitin sulfates. Most ligand-binding sites are within the 190 kDa isoform, which contains approximately 25 kDa of N-glycans and is the C-terminal half of the full-length 315 kDa HARE. Glycoproteomic analyses of purified recombinant human 190-HARE ecto-domain identified a diverse population of glycans at 10 of 17 consensus sites. The most diversity (and the only sialylated structures) occurred at N(2280), within the HA-binding Link domain. To determine if these N-glycans are required for HA binding, we created human Flp-In 293 cell lines expressing membrane-bound or soluble ecto-domain variants of 190-HARE(N2280A). Membrane-bound HARE lacking Link domain N-glycans mediated rapid HA endocytosis, but purified 190-HARE(N2280A) ecto-domain showed little or no HA binding in ELISA-like, HA-HARE pull-down assays or by surface plasmon resonance analysis (which detected very high apparent affinity for 190-HARE ecto-domain binding to HA; K(d) = 5.2 nM). The results indicate that Link domain N-glycans stabilize interactions that facilitate HA binding to HARE.
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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 |
Aug
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pubmed:issn |
1460-2423
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
991-1001
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pubmed:dateRevised |
2011-8-2
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pubmed:meshHeading |
pubmed-meshheading:20466649-Binding Sites,
pubmed-meshheading:20466649-Cell Adhesion Molecules, Neuronal,
pubmed-meshheading:20466649-Cell Line,
pubmed-meshheading:20466649-Endocytosis,
pubmed-meshheading:20466649-Humans,
pubmed-meshheading:20466649-Hyaluronic Acid,
pubmed-meshheading:20466649-Polysaccharides,
pubmed-meshheading:20466649-Protein Structure, Tertiary
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pubmed:year |
2010
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pubmed:articleTitle |
N-Glycans on the link domain of human HARE/Stabilin-2 are needed for hyaluronan binding to purified ecto-domain, but not for cellular endocytosis of hyaluronan.
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pubmed:affiliation |
Department of Biochemistry & Molecular Biology and The Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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