Platelet receptor redox regulation
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Several recent findings point to an important role for redox regulation of platelet responses to collagen involving the receptor, glycoprotein (GP)VI. First, the antioxidant dietary compound, quercetin, was shown to inhibit GPVI-dependent platelet activation and signaling responses to collagen. Second, collagen increased platelet production of the oxygen radical, superoxide anion (O2.-), mediated by the multi-subunit enzyme nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidase. In that case, O 2.- was implicated in regulating not initial aggregation, but collagen-induced thrombus stabilization involving release of ADP. Third, our laboratory showed that an unpaired thiol in the GPVI cytoplasmic tail undergoes rapid oxidation to form GPVI homodimers following ligand binding, preceding GPVI signaling and ectodomain metalloproteolysis, and indicating formation of an oxidative submembranous environment in activated platelets. This review examines receptor/redox regulation in other cells, and relevance to the pathophysiological function of GPVI and other platelet receptors initiating thrombus formation in haemostasis or thrombotic diseases such as heart attack and stroke. © 2008 Informa UK Ltd.
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Walsh, T.; Berndt, Michael; Carrim, N.; Cowman, J.; Kenny, D.; Metharom, Pat (2014)Background: Activation of the platelet-specific collagen receptor, glycoprotein (GP) VI, induces intracellular reactive oxygen species (ROS) production; however the relevance of ROS to GPVI-mediated platelet responses ...
Activation of phosphatidylinositol 3-kinase ß by the platelet collagen receptors integrin a2ß1 and GPVI: The role of Pyk2 and c-CblManganaro, D.; Consonni, A.; Guidetti, G.; Canobbio, I.; Visconte, C.; Kim, S.; Okigaki, M.; Falasca, Marco; Hirsch, E.; Kunapuli, S.; Torti, M. (2015)Phosphatidylinositol 3-kinaseβ (PI3Kβ) plays a predominant role in integrin outside-in signaling and in platelet activation by GPVI engagement. We have shown that the tyrosine kinase Pyk2 mediates PI3Kβ activation downstream ...
Role of Focal Adhesion Tyrosine Kinases in GPVI-Dependent Platelet Activation and Reactive Oxygen Species FormationCarrim, N.; Walsh, T.; Consonni, A.; Torti, M.; Berndt, Michael; Metharom, Pat (2014)BackgroundWe have previously shown the presence of a TRAF4/p47phox/Hic5/Pyk2 complex associated with the platelet collagen receptor, GPVI, consistent with a potential role of this complex in GPVI-dependent ROS formation. ...