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.

Classification

There are 4 known protease-activated receptors or PARs, 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

PARs are activated by the action of serine proteases such as thrombin (acts on PARs 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.

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.

External links

• "Protease-Activated Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 
• MeSH Proteinase-Activated+Receptors

de:Protease-aktivierter Rezeptor