Thrombin cleaves its receptor at arginine-41, resulting in the generation of a new receptor NH2-terminus with the sequence Sfllrnpndkyepf. This peptide (TRP-14) may signal a variety of thrombin's responses. Sfllrnpndkyepf, representing the 14 amino acids starting with Ser-42 of the human thrombin receptor, was found to mimic the effect of thrombin on platelets. Cleavage of the human platelet thrombin receptor by thrombin exposes a new N-terminal which acts as a putative tethered ligand. Sfllrnpndkyepf, corresponding to the new N-terminal region, activates and induces platelet aggregation and serotonin secretion. Sfllrnpndkyepf is the minimal peptide length which retains full activity in inducing [ ¹⁴ C]serotonin secretion. TRAP induces rapid morphological changes in HUVECs, with marked increase in the release of prostacyclin, endothelin, platelet activating factor, tissue type plasminogen activator, and plasminogen activator inhibitor-1. Incubation of cells with TRAP also induces a rapid decrease in cell-surface thrombomodulin.