thrombin signaling and protease-activated receptors
| PAG Title | thrombin signaling and protease-activated receptors |
| PAG ID | WAG000219 |
| Type | P |
| Source Link |  BioCarta |
| Publication Reference | NA |
| PAG Description | Thrombin is an extracellular protease that is involved in the clotting of blood and inflammation through its action on platelets and endothelial cells in the vasculature and that plays a role in thrombosis and myocardial infarction. The protease activated receptors PAR1 and PAR4 are cellular targets of thrombin sigling and members of the G-protein coupled receptor gene family. Both of these receptors are cleaved in their N-terminus by thrombin, unmasking a portion of the receptor sequence that acts itself as a tethered peptide ligand that activates the receptor. The tethered ligand that activates PAR1 is SFLLRN and the tethered ligand that activates PAR4 is GYPGQV. Other members of the family include PAR2 which is activated by trypsin rather than thrombin and PAR3 which seems to play a role in the activation of other PARs but does not itself transduce a sigl directly. Addition of peptide agonist exogenously in solution can also activate PAR1, PAR2 and PAR4. PAR1 activation may be involved in the dilation of arteries during inflammation through the action of thrombin on endothelial cells and in platelet activation by thrombin during clotting. PAR1 and PAR2 activation cause bronchodilation in airway and may protect against asthma. PAR 4 activation by thrombin activates platelets during clotting and mice lacking PAR4 have impaired clotting and platelets that do not respond to thrombin sigling. The action of thrombin on PAR1 and PAR4 on platelets and endothelial cells may also contribute to vascular permeability and inflammation. |
| Species | Homo sapiens |
| nCoCo Score | 1,816 |
| Base PAG ID | WAG000219 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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