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Publication : Canonical Wnt signaling negatively regulates platelet function.

First Author  Steele BM Year  2009
Journal  Proc Natl Acad Sci U S A Volume  106
Issue  47 Pages  19836-41
PubMed ID  19901330 Mgi Jnum  J:154748
Mgi Id  MGI:4398768 Doi  10.1073/pnas.0906268106
Citation  Steele BM, et al. (2009) Canonical Wnt signaling negatively regulates platelet function. Proc Natl Acad Sci U S A 106(47):19836-41
abstractText  Wnts regulate important intracellular signaling events, and dysregulation of the Wnt pathway has been linked to human disease. Here, we uncover numerous Wnt canonical effectors in human platelets where Wnts, their receptors, and downstream signaling components have not been previously described. We demonstrate that the Wnt3a ligand inhibits platelet adhesion, activation, dense granule secretion, and aggregation. Wnt3a also altered platelet shape change and inhibited the activation of the small GTPase RhoA. In addition, we found the Wnt-beta-catenin signaling pathway to be functional in platelets. Finally, disruption of the Wnt Frizzled 6 receptor in the mouse resulted in a hyperactivatory platelet phenotype and a reduced sensitivity to Wnt3a. Taken together our studies reveal a novel functional role for Wnt signaling in regulating anucleate platelet function and may provide a tractable target for future antiplatelet therapy.
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