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• W2034019654 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 Fcγ receptor IIa (FcγRIIa) and glycoprotein VI (GPVI)/FcR γ-chain signaling pathways in platelets, its physiologic role in integrin αIIbβ3–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 αIIbβ3 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 αIIbβ3–mediated platelet aggregation. This functional integrin αIIbβ3 defect could not be attributed to altered expression of integrin αIIbβ3. 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 αIIbβ3 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 αIIbβ3–mediated platelet function and that disruption of PECAM-1 induced a moderate “outsidein” integrin αIIbβ3 signaling defect." @default.
• W2034019654 created "2016-06-24" @default.
• W2034019654 creator A5012548112 @default.
• W2034019654 creator A5025363666 @default.
• W2034019654 date "2005-12-01" @default.
• W2034019654 modified "2023-09-30" @default.
• W2034019654 title "The Ig-ITIM superfamily member PECAM-1 regulates the “outside-in” signaling properties of integrin αIIbβ3 in platelets" @default.
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• W2034019654 doi "https://doi.org/10.1182/blood-2005-03-0911" @default.
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