title: Regulation of β-catenin stabilization in human platelets.
abstract: The Wnt/β-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 β-catenin, which was abrogated upon depletion of calcium from platelet suspension. β-catenin cleavage was disallowed in absence of aggregation, thus implicating integrin αIIbβ3 engagement in β-catenin proteolysis. Degradation of β-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 β-catenin degradation. Thus activities of proteasome, calpain and protein kinase C regulate stabilization of β-catenin in aggregated human platelets.
authors: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, UP, India.
authors: Sharda
authors: S
authors: Kumari
authors: Debabrata
authors: D
authors: Dash
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D002154:Calpain / Q000378:metabolism; D006801:Humans; D010974:Platelet Aggregation / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin; D011493:Protein Kinase C; D002154:Calpain; D046988:Proteasome Endopeptidase Complex