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Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs .
Protease-activated receptors (PAR) are a subfamily of related G protein-coupled receptors that are activated by cleavage of part of their extracellular domain. They are highly expressed in platelets , and also on endothelial cells , fibroblasts, immune cells, myocytes , neurons , and tissues that line the gastrointestinal tract.
Thrombopoietin is a glycoprotein hormone produced by the liver and kidney which regulates the production of platelets. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that bud off large numbers of platelets. [5] Megakaryocytopoiesis is the cellular development process that leads to platelet production.
Platelets secrete thromboxane A2, which acts on the platelet's own thromboxane receptors on the platelet surface (hence the so-called "out-in" mechanism), and those of other platelets. These receptors trigger intraplatelet signaling, which converts GPIIb/IIIa receptors to their active form to initiate aggregation .
PAR1 is a G protein-coupled receptor and one of four protease-activated receptors involved in the regulation of thrombotic response. Highly expressed in platelets and endothelial cells, PAR1 plays a key role in mediating the interplay between coagulation and inflammation , which is important in the pathogenesis of inflammatory and fibrotic lung ...
In a quiescent platelet, P-selectin is located on the inner wall of α-granules. Platelet activation (through agonists such as thrombin, Type II collagen and ADP) results in "membrane flipping" where the platelet releases α- and dense granules and the inner walls of the granules are exposed on the outside of the cell.