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Thrombin Signaling

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Thrombin is a multifunctional serine protease involved in a number of pathophysiological processes that include blood clotting, inflammation, repair processes and tumor metastasis. In brain, thrombin regulates the viability of neurons and astrocytes by increasing survival under conditions of hypoglycemia and oxidative stress and inducing apoptosis under other conditions. Thrombin is also chemotactic for macrophages and mitogenic for smooth muscle cells, fibroblasts, and astrocytes and induces secretion of growth factors and cytokines from fibroblasts and smooth muscle cells. Most of the thrombin-mediated effects are preceded by morphological changes in cells that follow activation of PARs (Protease-Activated Receptors) (Ref.1).

PARs are a unique class of heterotrimeric, transmembrane GPCRs (G-Protein Coupled Receptors) activated by serine proteases that cleave specific regions of the [...]


1.Thrombin receptors activate G(o) proteins in endothelial cells to regulate intracellular calcium and cell shape changes.
Vanhauwe JF, Thomas TO, Minshall RD, Tiruppathi C, Li A, Gilchrist A, Yoon EJ, Malik AB, Hamm HE.
J Biol Chem. 2002 Sep 13;277(37):34143-9. Epub 2002 May 30.
2.Protease-activated receptor-1 stimulates Ca(2+)-dependent Cl(-) secretion in human intestinal epithelial cells.
Buresi MC, Schleihauf E, Vergnolle N, Buret A, Wallace JL, Hollenberg MD, MacNaughton WK.
Am J Physiol Gastrointest Liver Physiol. 2001 Aug;281(2):G323-32.
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