Linked Life Data

19940238

Source:http://linkedlifedata.com/resource/pubmed/id/19940238

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2009-12-18
pubmed:abstractText
The immune receptor signaling pathway is used by nonimmune cells, but the molecular adaptations that underlie its functional diversification are not known. Circulating platelets use the immune receptor homologue glycoprotein VI (GPVI) to respond to collagen exposed at sites of vessel injury. In contrast to immune cell responses, platelet activation must take place within seconds to successfully form thrombi in flowing blood. Here, we show that the GPVI receptor utilizes a unique intracellular proline-rich domain (PRD) to accelerate platelet activation, a requirement for efficient platelet adhesion to collagen under flow. The GPVI PRD specifically binds the Src-family kinase Lyn and directly activates it, presumably through SH3 displacement. In resting platelets, Lyn is constitutively bound to GPVI in an activated state and platelets lacking Lyn exhibit defective collagen adhesion like that of platelets with GPVI receptors lacking the PRD. These findings define a molecular priming mechanism that enables an immune-type receptor to adopt a hemostatic function. These studies also demonstrate that active kinases can constitutively associate with immune-type receptors without initiating signal transduction before receptor ligation, consistent with a recent molecular model of immune receptor signaling in which receptor ligation is required to bring active kinases to their receptor substrates.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-10506151, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-11001066, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-11110698, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-11301007, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-11331578, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-11723134, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-11943772, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-12594225, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-12649139, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-12847105, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-15886326, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-16102042, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-16261174, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-16374509, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-16699593, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-16849330, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-17170121, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-18464734, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-18676880, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-18955485, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-19013279, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-3259335, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-7988556, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-9024665, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-9028946, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-9670039, http://linkedlifedata.com/resource/pubmed/commentcorrection/19940238-9741630
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21167-72
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Molecular priming of Lyn by GPVI enables an immune receptor to adopt a hemostatic role.
pubmed:affiliation
Department of Medicine, Division of Cardiology, Division of Hematology, Institute for Medicine and Engineering, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural