Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9975
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dc.contributor.authorWee, Janet Len
dc.contributor.authorJackson, Denise Een
dc.date.accessioned2015-05-15T23:16:37Z
dc.date.available2015-05-15T23:16:37Z
dc.date.issued2005-08-04en
dc.identifier.citationBlood 2005; 106(12): 3816-23en
dc.identifier.govdoc16081692en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/9975en
dc.description.abstractPrevious 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.isoenen
dc.subject.otherAnimalsen
dc.subject.otherAntigens, CD31.genetics.metabolismen
dc.subject.otherBlood Platelets.metabolism.pathologyen
dc.subject.otherBlotting, Westernen
dc.subject.otherFlow Cytometryen
dc.subject.otherImmunoprecipitationen
dc.subject.otherIntegrins.metabolismen
dc.subject.otherMiceen
dc.subject.otherMice, Knockouten
dc.subject.otherPlatelet Adhesiveness.physiologyen
dc.subject.otherPlatelet Aggregation.physiologyen
dc.subject.otherSignal Transduction.physiologyen
dc.titleThe Ig-ITIM superfamily member PECAM-1 regulates the "outside-in" signaling properties of integrin alpha(IIb)beta3 in platelets.en
dc.typeJournal Articleen
dc.identifier.journaltitleBlooden
dc.identifier.affiliationKronheimer Building, Austin Research Institute, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australiaen
dc.identifier.doi10.1182/blood-2005-03-0911en
dc.description.pages3816-23en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/16081692en
dc.type.austinJournal Articleen
item.openairetypeJournal Article-
item.fulltextWith Fulltext-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextopen-
item.cerifentitytypePublications-
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