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DC Field | Value | Language |
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dc.contributor.author | Wee, Janet L | en |
dc.contributor.author | Jackson, Denise E | en |
dc.date.accessioned | 2015-05-15T23:16:37Z | |
dc.date.available | 2015-05-15T23:16:37Z | |
dc.date.issued | 2005-08-04 | en |
dc.identifier.citation | Blood 2005; 106(12): 3816-23 | en |
dc.identifier.govdoc | 16081692 | en |
dc.identifier.other | PUBMED | en |
dc.identifier.uri | http://ahro.austin.org.au/austinjspui/handle/1/9975 | en |
dc.description.abstract | Previous studies have implicated the immunoglobulin (Ig)-immunoreceptor tyrosine-based inhibitory motif (ITIM) superfamily member platelet endothelial cell adhesion molecule-1 (PECAM-1) in the regulation of integrin function. While PECAM-1 has been demonstrated to play a role as an inhibitory coreceptor of immunoreceptor tyrosine-based activation motif (ITAM)-associated Fcgamma receptor IIa (FcgammaRIIa) and glycoprotein VI (GPVI)/FcR gamma-chain signaling pathways in platelets, its physiologic role in integrin alpha(IIb)beta3-mediated platelet function is unclear. In this study, we investigate the functional importance of PECAM-1 in murine platelets. Using PECAM-1-deficient mice, we show that the platelets have impaired "outside-in" integrin alpha(IIb)beta3 signaling with impaired platelet spreading on fibrinogen, failure to retract fibrin clots in vitro, and reduced tyrosine phosphorylation of focal adhesion kinase p125 (125FAK) following integrin alpha(IIb)beta3-mediated platelet aggregation. This functional integrin alpha(IIb)beta3 defect could not be attributed to altered expression of integrin alpha(IIb)beta3. PECAM-1-/- platelets displayed normal platelet alpha granule secretion, normal platelet aggregation to protease-activated receptor-4 (PAR-4), adenosine diphosphate (ADP), and calcium ionophore, and static platelet adhesion. In addition, PECAM-1-/- platelets displayed normal "inside-out" integrin alpha(IIb)beta3 signaling properties as demonstrated by normal agonist-induced binding of soluble fluoroscein isothiocyanate (FITC)-fibrinogen, JON/A antibody binding, and increases in cytosolic-free calcium and inositol (1,4,5)P3 triphosphate (IP3) levels. This study provides direct evidence that PECAM-1 is essential for normal integrin alpha(IIb)beta3-mediated platelet function and that disruption of PECAM-1 induced a moderate "outsidein" integrin alpha(IIb)beta3 signaling defect. | en |
dc.language.iso | en | en |
dc.subject.other | Animals | en |
dc.subject.other | Antigens, CD31.genetics.metabolism | en |
dc.subject.other | Blood Platelets.metabolism.pathology | en |
dc.subject.other | Blotting, Western | en |
dc.subject.other | Flow Cytometry | en |
dc.subject.other | Immunoprecipitation | en |
dc.subject.other | Integrins.metabolism | en |
dc.subject.other | Mice | en |
dc.subject.other | Mice, Knockout | en |
dc.subject.other | Platelet Adhesiveness.physiology | en |
dc.subject.other | Platelet Aggregation.physiology | en |
dc.subject.other | Signal Transduction.physiology | en |
dc.title | The Ig-ITIM superfamily member PECAM-1 regulates the "outside-in" signaling properties of integrin alpha(IIb)beta3 in platelets. | en |
dc.type | Journal Article | en |
dc.identifier.journaltitle | Blood | en |
dc.identifier.affiliation | Kronheimer Building, Austin Research Institute, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia | en |
dc.identifier.doi | 10.1182/blood-2005-03-0911 | en |
dc.description.pages | 3816-23 | en |
dc.relation.url | https://pubmed.ncbi.nlm.nih.gov/16081692 | en |
dc.type.austin | Journal Article | en |
item.openairetype | Journal Article | - |
item.fulltext | With Fulltext | - |
item.languageiso639-1 | en | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
Appears in Collections: | Journal articles |
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File | Description | Size | Format | |
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16081692.pdf | 408.33 kB | Adobe PDF | ![]() View/Open |
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