Structural and functional features of PARs This is a summary of the proteases that activate or inactive individual PARs, the sequences surrounding the proteolytic cleavage sites of each PAR family member, the human (h), mouse (m), rat (r), or Xenopus laevis (x) tethered ligand sequences, currently available PAR antagonists, and the chromosomal localization of individual PAR family members. References and further details are provided in the text.
| PAR-1 | PAR-2 | PAR-3 | PAR-4 | |
|---|---|---|---|---|
| Primary activating protease (EC50) | Thrombin (50 pM) | Trypsin (1 nM) | Thrombin (0.2 nM) | Thrombin (5 nM) |
| Tryptase (1 nM) | Trypsin (1 nM) | |||
| Other activating proteases | Trypsin | FXa | Trypsin | |
| FXa | TF/FVIIa | Plasmin | ||
| MT-SP1 | Cathepsin Ga | |||
| Bacterial proteases | ||||
| Der P3 D9 | ||||
| Inactivating proteases | Cathepsin G | Cathepsin G | ||
| Plasmin | Plasmin | |||
| Proteinase 3 | Proteinase 3 | |||
| Elastase | Elastase | |||
| TACE-like MMP | ||||
| Cleavage sequence | LDPR ↓ SFLLRN | SKGR ↓ SLIGKV | LPIK ↓ TFRGAP | PAPR ↓ YPGQV |
| VNPR ↓ SFFLRN | SKGR ↓ SLIGRL | LTIK ↓ SNGGP | PNPR ↓ YPGKF | |
| Tethered ligand sequence | SFLLRN (h) | SLIGKV (h) | TFRGAP (h) | GYPGQV (h) |
| SFLLRN (m, r) | SLIGRL (m, r) | SFNGGP (m) | GYPGKF (m) | |
| TFRIFD (x) | ||||
| Hirudin-like sequence | Yes | No | Yes | No |
| Agonist peptides (generally as amides) | SFLLRN | SLIGKV | None known | GYPGKF |
| TFLLRN | SLIGRL | AYPGKF | ||
| SFLLRN | tc-YGPKF | |||
| tc-LIGRLO | tc-LIGRL | |||
| Antagonists | BMS-200261 | |||
| RWJ-56110 | ||||
| Chromosome | 5q13 (h) | 5q13 (h) | 5q13 (h) | 19p12 (h) |
| 13D2 (m) | 13D2 (m) | 13D2 (m) | 8B3.3 (m) |
MMP, matrix metalloproteinase; TACE, tumor necrosis factor-α converting enzyme.
↵ a Results examining the role of PAR-4 as a cellular cathepsin G receptor are inconsistent (see text)