Thrombin is a serine protease that regulates the activity of many cell types including the activation of platelets after vascular injury. Thrombin functions are mediated by G-protein-coupled protease-activated receptors that are homologous to substance P and thyrotropin receptors. Thrombin receptors (PAR1, PAR3, and PAR4) are seven transmembrane domain proteins with large N-terminal exodomains that contain a thrombin cleavage site (LDPR/S). Thrombin binds to the exodomain and cleaves the peptide bond between Arg-41 and Ser-42. This unmasks a new N-terminus with the sequence SFLLRN that acts as a tethered ligand. SFLLRN binds to the body of the thrombin receptor leading to irreversable activation. Both phosphorylation of the thrombin receptor and internalization may uncouple downstream signaling. PAR1 protein is expressed in vascular endothelial cells, smooth muscle cells, and macrophages, while PAR1 mRNA is expressed at higher levels in neonatal rat brain and lower levels in skeletal muscle, liver, and kidney. Thus, G-protein signaling via thrombin receptors, like PAR1, may be important for a diverse array of cellular functions, such as platelet activation and neural development.
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注意事项:
1.Since applications vary, each investigator should titrate the reagent to obtain optimal results.
2.Caution: Sodium azide yields highly toxic hydrazoic acid under acidic conditions. Dilute azide compounds in running water before discarding to avoid accumulation of potentially explosive deposits in plumbing.