Source:http://linkedlifedata.com/resource/pubmed/id/10845885
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2000-6-22
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| pubmed:abstractText |
alpha-Thrombin stimulation of human platelets initiates inside-out signaling to integrin alpha(IIb)beta(3) (glycoprotein IIb/IIIa), resulting in the exposure of ligand binding sites. In the present study, the regulation of alpha(IIb)beta(3) via protein kinases was investigated in platelets permeabilized with streptolysin O by introducing peptides that interfere with these enzymes and with possible regulatory domains in the cytosolic tail of the beta(3) subunit. Compared with intact platelets, the permeabilized platelets preserved >80% of the aggregation, secretion, and alpha(IIb)beta(3) ligand binding capacity. The peptide YIYGSFK, a substrate for Src kinases, inhibited alpha-thrombin-induced ligand binding to alpha(IIb)beta(3), but a reversed peptide with Y-->F substitutions (KFSGFIF) had no effect. Ligand binding to alpha(IIb)beta(3) was also inhibited by the peptide RKRCLRRL, which binds irreversibly to the catalytic domain of protein kinase C. Peptides corresponding to parts of the protein C inhibitor and beta(2)-glycoprotein I were used as negative controls and failed to interfere with ligand binding. Possible target domains for protein kinases are present in the cytoplasmic tail of the beta(3) subunit. The LLITIHDR peptide, matching the membrane-proximal domain of beta(3) (residues 717 to 724), had no effect, but NNPLYKEA (residues 743 to 750), EATSTFTN (residues 749 to 756), and TNITYRGT (residues 755 to 762), which mimicked overlapping domains of the carboxy-terminal part of beta(3), reduced alpha-thrombin-induced ligand binding by 60+/-4%, 97+/-1%, and 97+/-2% (n=3) at 500 micromol/L peptide, respectively. These observations indicate that Src kinases and protein kinase C take part in inside-out signaling to integrin alpha(IIb)beta(3) and identify target domains in beta(3) that contribute to the regulation of this integrin.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrin,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrinogen,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Aggregation Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Glycoprotein GPIIb-IIIa...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Streptolysins,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin,
http://linkedlifedata.com/resource/pubmed/chemical/glycyl-arginyl-glycyl-aspartyl-serin...,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/streptolysin O
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
1079-5642
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
20
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1651-60
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:10845885-Amino Acid Sequence,
pubmed-meshheading:10845885-Bacterial Proteins,
pubmed-meshheading:10845885-Binding Sites,
pubmed-meshheading:10845885-Blood Platelets,
pubmed-meshheading:10845885-Cell Membrane Permeability,
pubmed-meshheading:10845885-Enzyme Inhibitors,
pubmed-meshheading:10845885-Fibrin,
pubmed-meshheading:10845885-Fibrinogen,
pubmed-meshheading:10845885-Fibronectins,
pubmed-meshheading:10845885-Humans,
pubmed-meshheading:10845885-Oligopeptides,
pubmed-meshheading:10845885-Peptides,
pubmed-meshheading:10845885-Platelet Aggregation Inhibitors,
pubmed-meshheading:10845885-Platelet Glycoprotein GPIIb-IIIa Complex,
pubmed-meshheading:10845885-Protein Kinase C,
pubmed-meshheading:10845885-Protein Kinase Inhibitors,
pubmed-meshheading:10845885-Streptolysins,
pubmed-meshheading:10845885-Thrombin,
pubmed-meshheading:10845885-src-Family Kinases
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| pubmed:year |
2000
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| pubmed:articleTitle |
Inhibition of platelet integrin alpha(IIb)beta(3) by peptides that interfere with protein kinases and the beta(3) tail.
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| pubmed:affiliation |
Laboratory for Thrombosis and Haemostasis, Department of Haematology, University Medical Center Utrecht and Institute for Biomembranes, Utrecht University, Utrecht, The Netherlands.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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