Linked Life Data

20600849

Source:http://linkedlifedata.com/resource/pubmed/id/20600849

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-8-17
pubmed:abstractText
Three different surface receptors mediate thrombin-induced activation and aggregation of human blood platelets: the protease activated receptors 1 and 4 (PAR1 and PAR4), and the glycoprotein (GP) Ibalpha of the GPIb-IX-V complex. However, their relative contribution in the stimulation of specific intracellular signaling pathways by thrombin remains largely controversial. In this work, we have shown that activation of PAR1 and PAR4 by thrombin or by selective activating peptides stimulated phospholipase C, tyrosine kinases, as well as the small GTPase Rap1b, promoted actin polymerization and cytoskeleton reorganization. When platelets were desensitized for both PAR1 and PAR4, high doses of thrombin, were unable to activate Rap1b, but produced a still evident stimulation of phospholipase C, as documented by the measurement of intracellular Ca(2+) mobilization and protein kinase C activation. These events were abrogated upon proteolysis of GPIbalpha by the metalloproteinase mocarhagin. In PAR1- and PAR4-desensitized platelets, thrombin also induced tyrosine phosphorylation of some substrates, but, surprisingly, this event was largely independent of GPIbalpha binding, as it persisted upon platelet treatment with mocarhagin. Similarly, thrombin-induced actin polymerization and cytoskeleton reorganization were only minimally altered upon PAR1 and PAR4 inactivation and GPIbalpha proteolysis. Interestingly, none of these events were elicited by enzymatically inactive thrombin. Finally we found that GPIbalpha cleavage reduced, but did not abrogate, platelet aggregation in PAR1- and PAR4-desensitized platelets. These results identify a novel pathway for platelet activation operated by thrombin independently of PAR1, PAR4 and GPIbalpha.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Actins, http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Chloromethyl Ketones, http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Platelet Glycoprotein GPIb-IX..., http://linkedlifedata.com/resource/pubmed/chemical/RAP1B protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, PAR-1, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Thrombin, http://linkedlifedata.com/resource/pubmed/chemical/Thrombin, http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases, http://linkedlifedata.com/resource/pubmed/chemical/mocarhagin, http://linkedlifedata.com/resource/pubmed/chemical/phenylalanyl-prolyl-arginine..., http://linkedlifedata.com/resource/pubmed/chemical/protease-activated receptor 4, http://linkedlifedata.com/resource/pubmed/chemical/rap GTP-Binding Proteins
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1873-3913
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1681-7
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Thrombin induces platelet activation in the absence of functional protease activated receptors 1 and 4 and glycoprotein Ib-IX-V.
pubmed:affiliation
Department of Biochemistry, University of Pavia, via Bassi 21, 27100 Pavia, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't