F2RL3 explained

Protease-activated receptor 4 (PAR-4), also known as coagulation factor II (thrombin) receptor-like 3, is a protein that in humans is encoded by the F2RL3 gene.^[1]

Function

Coagulation factor II (thrombin) receptor-like 3 (F2RL3) is a member of the large family of 7-transmembrane-region receptors that couple to guanosine-nucleotide-binding proteins. F2RL3 is also a member of the protease-activated receptor family. F2RL3 is activated by proteolytic cleavage of its extracellular amino terminus. The new amino terminus functions as a tethered ligand and activates the receptor. F2RL3 is activated by thrombin and trypsin.

See also

• Protease-activated receptor

Further reading

• Leger AJ, Covic L, Kuliopulos A . Protease-activated receptors in cardiovascular diseases. . Circulation . 114 . 10 . 1070–7 . 2006 . 16952995 . 10.1161/CIRCULATIONAHA.105.574830 . 312800 . free .
• Xu WF, Andersen H, Whitmore TE . Cloning and characterization of human protease-activated receptor 4. . Proc. Natl. Acad. Sci. U.S.A. . 95 . 12 . 6642–6 . 1998 . 9618465 . 10.1073/pnas.95.12.6642 . 22580 . 1998PNAS...95.6642X . etal. free .
• Kahn ML, Zheng YW, Huang W . A dual thrombin receptor system for platelet activation. . Nature . 394 . 6694 . 690–4 . 1998 . 9716134 . 10.1038/29325 . 1998Natur.394..690K . 4408582 . etal.
• Kahn ML, Hammes SR, Botka C, Coughlin SR . Gene and locus structure and chromosomal localization of the protease-activated receptor gene family. . J. Biol. Chem. . 273 . 36 . 23290–6 . 1998 . 9722561 . 10.1074/jbc.273.36.23290 . 32777201 . free .
• Kahn ML, Nakanishi-Matsui M, Shapiro MJ . Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. . J. Clin. Invest. . 103 . 6 . 879–87 . 1999 . 10079109 . 10.1172/JCI6042 . 408153 . etal.
• Andersen H, Greenberg DL, Fujikawa K . Protease-activated receptor 1 is the primary mediator of thrombin-stimulated platelet procoagulant activity. . Proc. Natl. Acad. Sci. U.S.A. . 96 . 20 . 11189–93 . 1999 . 10500152 . 10.1073/pnas.96.20.11189 . 18009 . 1999PNAS...9611189A . etal. free .
• Sambrano GR, Huang W, Faruqi T . Cathepsin G activates protease-activated receptor-4 in human platelets. . J. Biol. Chem. . 275 . 10 . 6819–23 . 2000 . 10702240 . 10.1074/jbc.275.10.6819 . 33219053 . etal. free .
• Nakanishi-Matsui M, Zheng YW, Sulciner DJ . PAR3 is a cofactor for PAR4 activation by thrombin. . Nature . 404 . 6778 . 609–13 . 2000 . 10766244 . 10.1038/35007085 . 2000Natur.404..609N . 4410800 . etal.
• Miike S, McWilliam AS, Kita H . Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2. . J. Immunol. . 167 . 11 . 6615–22 . 2002 . 11714832 . 10.4049/jimmunol.167.11.6615. 9302877 . free .
• Asokananthan N, Graham PT, Fink J . Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells. . J. Immunol. . 168 . 7 . 3577–85 . 2002 . 11907122 . 10.4049/jimmunol.168.7.3577. 45171728 . etal. free .
• Henriksen RA, Hanks VK . PAR-4 agonist AYPGKF stimulates thromboxane production by human platelets. . Arterioscler. Thromb. Vasc. Biol. . 22 . 5 . 861–6 . 2002 . 12006403 . 10.1161/01.ATV.0000014742.56572.25 . 24246544 . free .
• Covic L, Singh C, Smith H, Kuliopulos A . Role of the PAR4 thrombin receptor in stabilizing platelet-platelet aggregates as revealed by a patient with Hermansky-Pudlak syndrome. . Thromb. Haemost. . 87 . 4 . 722–7 . 2003 . 12008957 . 10.1055/s-0037-1613071. 32831294 .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Owen WG . PAR-3 is a low-affinity substrate, high affinity effector of thrombin. . Biochem. Biophys. Res. Commun. . 305 . 1 . 166–8 . 2003 . 12732212 . 10.1016/S0006-291X(03)00732-0 .
• Adam F, Verbeuren TJ, Fauchère JL . Thrombin-induced platelet PAR4 activation: role of glycoprotein Ib and ADP. . J. Thromb. Haemost. . 1 . 4 . 798–804 . 2003 . 12871418 . 10.1046/j.1538-7836.2003.00138.x . 12762388 . etal. free .
• Wu CC, Hwang TL, Liao CH . The role of PAR4 in thrombin-induced thromboxane production in human platelets. . Thromb. Haemost. . 90 . 2 . 299–308 . 2004 . 12888878 . 10.1160/TH03-02-0103 . 4983617 . etal.
• Kawai T, Akira S, Reed JC . ZIP kinase triggers apoptosis from nuclear PML oncogenic domains. . Mol. Cell. Biol. . 23 . 17 . 6174–86 . 2003 . 12917339 . 10.1128/MCB.23.17.6174-6186.2003 . 180930 .
• Jacques SL, Kuliopulos A . Protease-activated receptor-4 uses dual prolines and an anionic retention motif for thrombin recognition and cleavage. . Biochem. J. . 376 . Pt 3 . 733–40 . 2004 . 13678420 . 10.1042/BJ20030954 . 1223816 .
• Han Y, Nurden A, Combrié R, Pasquet JM . Redistribution of glycoprotein Ib within platelets in response to protease-activated receptors 1 and 4: roles of cytoskeleton and calcium. . J. Thromb. Haemost. . 1 . 10 . 2206–15 . 2004 . 14521606 . 10.1046/j.1538-7836.2003.00436.x . 24420859 . free .

Notes and References

1. Web site: Entrez Gene: F2RL3 coagulation factor II (thrombin) receptor-like 3.