Regulation of Neurons and Astrocytes by Thrombin and Protease Nexin-1

Autor: Dennis D. Cunningham, Frances M. Donovan
Rok vydání: 1997
Předmět:
Zdroj: Advances in Experimental Medicine and Biology ISBN: 9781461374619
Popis: Thrombin is best known for its pivotal role as the final protease in the blood coagulation cascade and its ability to cleave fibrinogen to fibrin and to cause platelet aggregation. Studies over the past twenty or so years have shown that in addition thrombin regulates a number of important activities of cells that may be important in repair processes following injury. The first demonstration of a cell regulatory role for thrombin came from landmark studies by Chen and Buchanan who showed that thrombin is a potent mitogen for cultured fibroblasts1. Subsequently, much effort was directed at understanding the mechanisms by which thrombin regulates certain cells. Early studies identified cell surface receptors for thrombin2 and showed that the proteolytic activity of thrombin was required for cell activation3. A major advance in understanding the mechanism of cellular regulation by thrombin was the cloning of the cDNA for the thrombin receptor4,5. These studies revealed that the thrombin receptor is a seven transmembrane G protein-coupled receptor that is activated by proteolytic cleavage. This novel activation mechanism produces a new extracellular amino terminus which serves as a tethered ligand which binds back to the receptor and activates it. This was demonstrated by the finding that a peptide representing the first six amino acids of the newly produced amino terminus of the receptor (SFLLRN) could fully activate the thrombin receptor4. The thrombin receptor has been shown subsequently to be present on a number of cell types and to mediate the cell regulatory effects of thrombin.
Databáze: OpenAIRE