Linked Life Data

10766244

Source:http://linkedlifedata.com/resource/pubmed/id/10766244

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6778
pubmed:dateCreated
2000-4-27
pubmed:abstractText
Identification of the mechanisms by which the coagulation protease thrombin activates platelets is critical for understanding haemostasis and thrombosis. Thrombin activates cells at least in part by cleaving protease-activated G-protein-coupled receptors (PARs). PAR3 and PAR4 are thrombin receptors expressed in mouse platelets. Inhibition of thrombin binding to mPAR3 (ref. 4) and knockout of the mPAR3 gene inhibited mouse platelet activation at low but not high concentrations of thrombin. Thus PAR3 is important for thrombin signalling in mouse platelets. Expression of human PAR3 in heterologous expression systems reliably resulted in responsiveness to thrombin. Curiously, despite its importance for the activation of mouse platelets by thrombin, mouse PAR3 (mPAR3) did not lead to thrombin signalling even when overexpressed. We now report that mPAR3 and mPAR4 interact in a novel way: mPAR3 does not itself mediate transmembrane signalling but instead functions as a cofactor for the cleavage and activation of mPAR4 by thrombin. This establishes a paradigm for cofactor-assisted PAR activation and for a G-protein-coupled receptor's acting as an accessory molecule to present ligand to another receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0028-0836
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
404
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
609-13
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
PAR3 is a cofactor for PAR4 activation by thrombin.
pubmed:affiliation
Cardiovascular Research Institute and Daiichi Research Center, University of California, San Francisco 94143-0130, USA.
pubmed:publicationType
Journal Article