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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1994-11-23
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pubmed:abstractText |
Integrins and other adhesion receptors are essential components for outside-in and inside-out signaling through the cell membrane. The platelet glycoprotein IIb-IIIa (also known as fibrinogen receptor or integrin alpha IIb beta 3) is activated by platelet agonists, inhibited by cyclic-nucleotide-elevating agents, and is involved in the activation of protein tyrosine kinases including the 125-kDa focal adhesion kinase (pp125FAK). However, the molecular details of glycoprotein IIb-IIIa regulation are not well understood. Here we report that in ADP-activated human platelets cAMP- and cGMP-dependent protein-kinase-mediated phosphorylation of the focal adhesion vasodilator-stimulated phosphoprotein (VASP) at Ser157 correlates well with glycoprotein IIb-IIIa inhibition. Human platelets contain similar concentrations of glycoprotein IIb-IIIa complexes (fibrinogen binding sites) and VASP. Using gel-filtered platelets, cAMP-elevating agents [e.g. prostaglandin E1 and the forskolin analog 6-(3-dimethylaminopropionyl)forskolin (NKH 477)] caused VASP Ser157 phosphorylation and inhibited glycoprotein IIb-IIIa activation up to 70-100%. NO-generating, cGMP-elevating agents [e.g. 3-morpholinosydnonimine hydrochloride (SIN1) and sodium nitroprusside] stimulated VASP Ser157 phosphorylation and inhibited glycoprotein IIb-IIIa activation up to a maximal extent of 30-50%. The effects of cAMP- and cGMP-elevating agents on VASP phosphorylation and fibrinogen binding were reversible and could be mimicked by membrane-permeant selective activators of platelet cAMP- or cGMP-dependent protein kinase, respectively. Using threshold concentrations, the nitrovasodilator SIN 1 potentiated the effects of the forskolin analog NKH 477 with respect to inhibition of platelet aggregation, VASP phosphorylation and glycoprotein IIb-IIIa inhibition. It is proposed that the inhibition of glycoprotein IIb-IIIa induced by cyclic nucleotide involves cAMP-and cGMP-dependent protein-kinase-mediated VASP phosphorylation at Ser157.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-morpholino-sydnonimine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Alprostadil,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Protein-Tyrosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Molsidomine,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroprusside,
http://linkedlifedata.com/resource/pubmed/chemical/PTK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents,
http://linkedlifedata.com/resource/pubmed/chemical/colforsin,
http://linkedlifedata.com/resource/pubmed/chemical/vasodilator-stimulated...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0014-2956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
225
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
21-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7925440-Adenosine Diphosphate,
pubmed-meshheading:7925440-Alprostadil,
pubmed-meshheading:7925440-Blood Platelets,
pubmed-meshheading:7925440-Blood Proteins,
pubmed-meshheading:7925440-Cell Adhesion Molecules,
pubmed-meshheading:7925440-Focal Adhesion Kinase 1,
pubmed-meshheading:7925440-Focal Adhesion Protein-Tyrosine Kinases,
pubmed-meshheading:7925440-Forskolin,
pubmed-meshheading:7925440-Humans,
pubmed-meshheading:7925440-Kinetics,
pubmed-meshheading:7925440-Membrane Proteins,
pubmed-meshheading:7925440-Microfilament Proteins,
pubmed-meshheading:7925440-Molsidomine,
pubmed-meshheading:7925440-Nitroprusside,
pubmed-meshheading:7925440-Phosphoproteins,
pubmed-meshheading:7925440-Phosphoserine,
pubmed-meshheading:7925440-Platelet Membrane Glycoproteins,
pubmed-meshheading:7925440-Protein Kinases,
pubmed-meshheading:7925440-Protein-Tyrosine Kinases,
pubmed-meshheading:7925440-Serine,
pubmed-meshheading:7925440-Vasodilator Agents
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pubmed:year |
1994
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pubmed:articleTitle |
Phosphorylation of focal adhesion vasodilator-stimulated phosphoprotein at Ser157 in intact human platelets correlates with fibrinogen receptor inhibition.
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pubmed:affiliation |
Medizinische Universitätsklinik, Klinische Forschergruppe, Würzburg, Germany.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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