Thrombin recognizes the N-terminal exodomain of PAR1 by interacting with sites both amino and carboxyl terminal to the thrombin cleavage site. Thrombin cleaves the peptide bond between receptor residues Arg41 and Ser42. This serves to unmask a new amino terminus beginning with the sequence SFLLRN that functions as a tethered ligand, docking intramolecularly with the body of the receptor to effect transmembrane signaling. A synthetic peptide of sequence SFLLRN, which mimics the tethered ligand sequence, will function as an agonist for PAR1 independent of receptor cleavage. Thus PAR1 is, in essence, a peptide receptor that carries its own ligand, the latter being active only after receptor cleavage.