Protease-activated receptor
| coagulation factor II (thrombin) receptor | |
|---|---|
| Identifiers | |
| Symbol | F2R |
| Alt. symbols | PAR1 |
| Entrez | 2149 |
| HUGO | 3537 |
| OMIM | 187930 |
| RefSeq | NM_001992 |
| UniProt | P25116 |
| Other data | |
| Locus | Chr. 5 q13 |
| coagulation factor II (thrombin) receptor-like 1 | |
|---|---|
| Identifiers | |
| Symbol | F2RL1 |
| Alt. symbols | PAR2, GPR11 |
| Entrez | 2150 |
| HUGO | 3538 |
| OMIM | 600933 |
| RefSeq | NM_005242 |
| UniProt | P55085 |
| Other data | |
| Locus | Chr. 5 q13 |
| coagulation factor II (thrombin) receptor-like 2 | |
|---|---|
| Identifiers | |
| Symbol | F2RL2 |
| Alt. symbols | PAR3 |
| Entrez | 2151 |
| HUGO | 3539 |
| OMIM | 601919 |
| RefSeq | NM_004101 |
| UniProt | O00254 |
| Other data | |
| Locus | Chr. 5 q13 |
| coagulation factor II (thrombin) receptor-like 3 | |
|---|---|
| Identifiers | |
| Symbol | F2RL3 |
| Alt. symbols | PAR4 |
| Entrez | 9002 |
| HUGO | 3540 |
| OMIM | 602779 |
| RefSeq | NM_003950 |
| UniProt | Q96RI0 |
| Other data | |
| Locus | Chr. 19 p12 |
Protease-activated receptors are a subfamily of related G protein-coupled receptors that are activated by cleavage of part of their extracellular domain. They are highly expressed in platelets, but also on endothelial cells, myocytes and neurons.[1]
Classification
There are 4 known protease-activated receptors or PAR's, numbered from one to four. These receptors are members of the seven transmembrane G-protein-coupled receptor superfamily, and are expressed throughout the body.
Activation
PAR's are activated by the action of serine proteases such as thrombin (acts on PAR's 1, 3 and 4) and trypsin (PAR 2). These enzymes cleave the N-terminus of the receptor, which in turn acts as a tethered ligand. In the cleaved state, part of the receptor itself acts as the agonist, causing a physiological response.
Most of the PAR family act through the actions of G-proteins i (cAMP inhibitory), 12/13 (Raf/Ras activation) and q (calcium signalling) to cause cellular actions.
Function
The cellular effects of thrombin are mediated by protease-activated receptors (PARs). Thrombin signalling in platelets contributes to hemostasis and thrombosis. Endothelial PARs participate in the regulation of vascular tone and permeability while in vascular smooth muscle they mediate contraction, proliferation, and hypertrophy. PARs contribute to the pro-inflammatory response observed in atherosclerosis and restenosis. Recent research has also implicated these novel receptors in muscle growth and bone cell differentiation and proliferation.[2]
In T cells, activation of PAR1, PAR2 and PAR3 induce tyrosine phosphorylation of VAV1. Activation of PARs also led to an increase in tyrosine phosphorylation of ZAP-70 and SLP-76, two key proteins in T cell receptor (TCR) signalling.[3]
References
- ↑ Macfarlane SR, Seatter MJ, Kanke T, Hunter GD, Plevin R (2001). "Proteinase-activated receptors". Pharmacol Rev. 53 (2): 245–82. PMID 11356985.
- ↑ Martorell L, Martínez-González J, Rodríguez C, Gentile M, Calvayrac O, Badimon L (February 2008). "Thrombin and protease-activated receptors (PARs) in atherothrombosis". Thromb. Haemost. 99 (2): 305–15. doi:10.1160/TH07-08-0481. PMID 18278179.
- ↑ Bar-Shavit R, Maoz M, Yongjun Y, Groysman M, Dekel I, Katzav S (January 2002). "Signalling pathways induced by protease-activated receptors and integrins in T cells". Immunology. 105 (1): 35–46. doi:10.1046/j.0019-2805.2001.01351.x. PMC 1782632. PMID 11849313.
External links
- IUPHAR GPCR Database - Protease-activated receptors
- Proteinase-Activated+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
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