Linked Life Data

11279169

Source:http://linkedlifedata.com/resource/pubmed/id/11279169

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2001-5-23
pubmed:abstractText
Glycoprotein I(b)alpha (GP I(b)alpha), the ligand binding subunit of the platelet glycoprotein Ib-IX-V complex, is sulfated on three tyrosine residues (Tyr-276, Tyr-278, and Tyr-279). This posttranslational modification is known to be critical for von Willebrand factor (vWF) binding; yet it remains unclear whether it provides a specific structure or merely contributes negative charges. To investigate this issue, we constructed cell lines expressing GP I(b)alpha polypeptides with the three tyrosine residues converted to either Glu or Phe and studied the ability of these mutants to bind vWF in the presence of modulators or shear stress. The mutants were expressed normally on the cell surface as GP Ib-IX complexes, with the conformation of the ligand-binding domain preserved, as judged by the binding of conformation-sensitive monoclonal antibodies. In contrast to their normal expression, both mutants were functionally abnormal. Cells expressing the Phe mutant failed to bind vWF in the presence of either ristocetin or botrocetin. These cells adhered to and rolled on immobilized vWF only when their surface receptor density was increased to twice the level that supported adhesion of cells expressing the wild-type receptor and even then only 20% as many rolled and rolled significantly faster than wild-type cells. Cells expressing the Glu mutant, on the other hand, were normal with respect to ristocetin-induced vWF binding and adhesion to immobilized vWF but were markedly defective in botrocetin-induced vWF binding. These results indicate that GP I(b)alpha tyrosine sulfation influences the interaction of this polypeptide with vWF primarily by contributing negative charges under physiological conditions and when the interaction is induced by ristocetin but contributes a specific structure to the botrocetin-induced interaction.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16690-4
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11279169-Amino Acid Sequence, pubmed-meshheading:11279169-Amino Acid Substitution, pubmed-meshheading:11279169-Binding Sites, pubmed-meshheading:11279169-Cell Adhesion, pubmed-meshheading:11279169-Cell Line, pubmed-meshheading:11279169-Crotalid Venoms, pubmed-meshheading:11279169-Glutamic Acid, pubmed-meshheading:11279169-Hemagglutinins, pubmed-meshheading:11279169-Humans, pubmed-meshheading:11279169-Kinetics, pubmed-meshheading:11279169-Ligands, pubmed-meshheading:11279169-Models, Molecular, pubmed-meshheading:11279169-Molecular Sequence Data, pubmed-meshheading:11279169-Mutagenesis, Site-Directed, pubmed-meshheading:11279169-Phenylalanine, pubmed-meshheading:11279169-Platelet Glycoprotein GPIb-IX Complex, pubmed-meshheading:11279169-Protein Structure, Secondary, pubmed-meshheading:11279169-Recombinant Proteins, pubmed-meshheading:11279169-Ristocetin, pubmed-meshheading:11279169-Stress, Mechanical, pubmed-meshheading:11279169-Transfection, pubmed-meshheading:11279169-Tyrosine, pubmed-meshheading:11279169-von Willebrand Factor
pubmed:year
2001
pubmed:articleTitle
Tyrosine sulfation of glycoprotein I(b)alpha. Role of electrostatic interactions in von Willebrand factor binding.
pubmed:affiliation
Division of Thrombosis Research, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't