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Signaling through the second messengers calcium and diacylglycerol (DAG) is a critical element in many biological systems. Integration of calcium and DAG signals has been suggested to occur primarily through protein kinase C family members, which bind both calcium and DAG. However, an alternative pathway may involve members of the CalDAG-GEF/RasGRP protein(More)
Interaction of the platelet receptor glycoprotein (GP) Ib-V-IX with von Willebrand factor exposed at a site of vascular injury is an essential step in the initiation of a hemostatic plug. Proteolytic cleavage (shedding) of the GPIbalpha subunit was first described >25 years ago, the protease mediating this event as well as its physiological function,(More)
GPIbalpha binding to von Willebrand factor (VWF) exposed at a site of vascular injury is thought to be the first step in the formation of a hemostatic plug. However, our previous studies in VWF-deficient mice demonstrated delayed but not absent arterial thrombus formation, suggesting that, under these conditions, GPIbalpha may bind other ligands or that a(More)
OBJECTIVE Plasma fibronectin (FN) is decreased in several clinical conditions. We were interested to study the thrombotic and hemostatic consequences of the decrease in plasma FN (pFN), the role of FN splice variants in thrombosis, and to examine whether pFN incorporates into thrombi in vivo. METHODS AND RESULTS We compared the thrombotic response to a(More)
Platelet interaction with subendothelial collagen is crucial for hemostasis and thrombosis. Under conditions of elevated shear, platelet adhesion and activation on collagen requires the coordinated action of glycoprotein (GP) Ib and GPVI, which may be physically and functionally linked in the platelet membrane. While the surface expression of GPIb can be(More)
Platelet transfusions are a crucial component of support for patients with severe thrombocytopenia. Storage of platelet concentrates, however, is associated with a reduction in platelet posttransfusion recovery and hemostatic function. In this study, we established a model of mitochondrial injury that resembles platelet storage lesion. Mitochondrial injury,(More)
Successful discovery of therapeutic antibodies hinges on the identification of appropriate affinity binders targeting a diversity of molecular epitopes presented by the antigen. Antibody campaigns that yield such broad "epitope coverage" increase the likelihood of identifying candidates with the desired biological functions. Accordingly, epitope binning(More)
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