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.
This antibody is routinely tested by western blot analysis. Other applications were tested at BD Biosciences Pharmingen during antibody development only or reported in the literature.