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How the protease thrombin talks to cells
Pages 11023-11027

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From page 11023...
... This new amino terminus then serves as a tethered peptide ligand, binding intramolecularly to the body of the receptor to effect transmembrane signaling. The irreversibility of PART's proteolytic activation mechanism stands in contrast to the reversible ligand binding that activates classical G protein-coupled receptors and compels special mechanisms for desensitization and desensitization.
From page 11024...
... These data suggest that the cytoplasmic tails of PART and substance P receptor specify distinct intracellular sorting patterns in a single cell type. More importantly, the "irreversible" thrombin signaling seen in cells expressing the P/S chimera suggests that lysosomal sorting is indeed necessary to prevent persistent signaling by activated PART.
From page 11025...
... Inhibition of PAR3 function with antibodies that bound to PAR3's hirudin-like domain or by gene knockout prevented mouse platelet activation by low but not high concentrations of thrombin (33, 45~. These results established that PAR3 is necessary for normal thrombin signaling in mouse platelets but also pointed to the existence of another platelet thrombin receptor.
From page 11026...
... Thrombin generation is triggered when factor VIIa in plasma meets extravascular tissue factor, hence the coagulation protease cascade can be viewed in part as a "leak detector" for blood vessels. Perhaps developing blood vessels use this system to monitor their functional status as they grow and remodel.
From page 11027...
... Colloquium Paper: Coughlin 46. Bernatowicz, M


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