Linked Life Data

1400429

Source:http://linkedlifedata.com/resource/pubmed/id/1400429

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
1992-11-18
pubmed:abstractText
von Willebrand factor (vWF) is a multimeric plasma glycoprotein that mediates platelet adhesion to the subendothelium via binding to platelet glycoprotein Ib (GPIb) and to components of the vessel wall. Recently, missense mutations that cause type IIB von Willebrand disease (vWD) were described, clustered within a disulfide loop in the A1 domain of vWF that has binding sites for GPIb, collagen, and heparin. In type IIB vWD, plasma vWF exhibits increased affinity for platelet GPIb, but decreased binding to collagen and heparin. The effect was studied of a type IIB vWD mutation, Arg578-->Gln, on the interaction of vWF with GPIb, collagen, and heparin. Recombinant wild type rvWF and mutant rvWF(R578Q) were expressed in COS-7 cells. Ristocetin-induced binding of rvWF(R578Q) to GPIb was markedly increased compared with rvWF, confirming that the Arg578-->Gln mutation causes the characteristic gain-of-function abnormality of type IIB vWD; botrocetin-induced binding was only slightly increased. Binding to collagen type III and heparin-agarose was compared for rvWF(R578Q) and plasma vWF from patients with four different type IIB mutations: Arg543-->Trp, Arg545-->Cys, Val553-->Met, Arg578-->Gln. For all of the plasma samples, binding to collagen and to heparin was reduced compared with normal plasma. In contrast, binding of rvWF(R578Q) to collagen and heparin was normal compared with wild type rvWF. Therefore, the Arg578-->Gln mutation increases the affinity of vWF for GPIb but does not directly impair vWF interaction with collagen or heparin. Arg578 may therefore be necessary to prevent normal vWF from interacting with GPIb. In type IIB vWD, the defective binding of plasma vWF to collagen and heparin may be secondary to post-synthetic modifications that occur in vivo, such as the loss of high molecular weight vWF multimers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21187-92
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:1400429-Amino Acid Sequence, pubmed-meshheading:1400429-Animals, pubmed-meshheading:1400429-Arginine, pubmed-meshheading:1400429-Base Sequence, pubmed-meshheading:1400429-Cell Line, pubmed-meshheading:1400429-Chromatography, Affinity, pubmed-meshheading:1400429-Cloning, Molecular, pubmed-meshheading:1400429-Collagen, pubmed-meshheading:1400429-Glutamine, pubmed-meshheading:1400429-Heparin, pubmed-meshheading:1400429-Humans, pubmed-meshheading:1400429-Kinetics, pubmed-meshheading:1400429-Membrane Glycoproteins, pubmed-meshheading:1400429-Molecular Sequence Data, pubmed-meshheading:1400429-Mutation, pubmed-meshheading:1400429-Oligodeoxyribonucleotides, pubmed-meshheading:1400429-Plasmids, pubmed-meshheading:1400429-Recombinant Proteins, pubmed-meshheading:1400429-Ristocetin, pubmed-meshheading:1400429-Transfection, pubmed-meshheading:1400429-von Willebrand Factor
pubmed:year
1992
pubmed:articleTitle
Recombinant von Willebrand factor Arg578-->Gln. A type IIB von Willebrand disease mutation affects binding to glycoprotein Ib but not to collagen or heparin.
pubmed:affiliation
Department of Medicine and Biochemistry, Jewish Hospital of St. Louis, Washington University School of Medicine, Missouri 63110.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.