Platelet Receptor Shedding
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Receptor shedding is a mechanism for irreversible removal of transmembrane cell surf.1ce receptors by proteolysis of the receptor at a position near the extracellular surface of the plasma membrane. This process generates a soluble ectodomain fragment and a membrane-associated remnant fragment, and is distinct from loss of receptor surface expression by internalization or microparticle release or secretion of alternatively spliced soluble forms of receptors lacking a transmembrane domain. There has been an increased focus on new methods for analyzing shedding of platelet glycoprotein (GP)Ib-IX-V and GPVI because these receptors are platelet specific and are critical for the initiation of platelet adhesion and activation in thrombus formation at arterial shear rates. Platelet receptor shedding provides a mechanism for downregulating surface expression resulting in loss of ligand binding, decreasing the surface density affecting receptor cross linking and signalling and generation of proteolytic fragments that may be functional and/ or provide platelet-specific biomarkers.
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Specific inhibition of ectodomain shedding of glycoprotein lba by targeting its juxtamembrane shedding cleavage siteLiang, X; Russell, S; Estelle, S; Jones, L; Cho, S; Khan, M; Berndt, Michael; Bunting, S; Ware, J; Li, R (2013)Background: Ectodomain shedding of glycoprotein Ibα (GPIbα), a proteolytic event in which metalloprotease ADAM17 cleaves the Gly464-Val465 bond and releases glycocalicin to the plasma, is considered a critical step in ...
Qiao, J.; Wu, Yong Hong; Wu, X.; Liu, Y.; Li, X.; Ju, W.; Qi, K.; Li, D.; Gardiner, E.; Andrews, R.; Zeng, L.; Xu, K. (2017)Increased risk of thromboembolism and platelet hyperreactivity has been reported in patients receiving thalidomide therapy. Whether thalidomide induces platelet activation directly or through other factors remains unclear. ...
Deng, W.; Xu, Y.; Chen, W.; Paul, D.; Syed, A.; Dragovich, M.; Liang, X.; Zakas, P.; Berndt, Michael; Di Paola, J.; Ware, J.; Lanza, F.; Doering, C.; Bergmeier, W.; Zhang, X.; Li, R. (2016)Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib-IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable ...