Regulation of β-catenin stabilization in human platelets

The Wnt/beta-catenin pathway controls developmental processes and homeostasis; however, abnormal activation of this pathway has been linked to several human diseases. Recent reports have demonstrated regulation of platelet function by canonical and non-canonical Wnt signalling. Platelet aggregation plays a crucial role in haemostasis and thrombosis. Here we report for the first time that, induction of sustained aggregation of platelets by a strong agonist in the presence of calcium was associated with nearly complete proteolysis of beta-catenin, which was abrogated upon depletion of calcium from platelet suspension. beta-catenin cleavage was disallowed in absence of aggregation, thus implicating integrin alpha(IIb)beta(3) engagement in beta-catenin proteolysis. Degradation of beta-catenin was blocked partially by inhibitors of either proteasome or calpain and completely when cells were exposed to both the inhibitors. Protein kinase C inhibition, too, abolished beta-catenin degradation. Thus activities of proteasome, calpain and protein kinase C regulate stabilization of beta-catenin in aggregated human platelets. (C) 2013 Elsevier Masson SAS. All rights reserved.