The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

F2rl3  -  coagulation factor II (thrombin) receptor...

Mus musculus

Synonyms: Coagulation factor II receptor-like 3, PAR-4, PAR4, Par4, Proteinase-activated receptor 4, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of F2rl3


High impact information on F2rl3


Chemical compound and disease context of F2rl3

  • The recent observation that knock-out of protease-activated receptor-4 (PAR4) ablates thrombin signaling in mouse platelets and protects against ferric chloride-induced thrombosis of mouse mesenteric arterioles suggests that thrombin's actions on platelets can play an important role in thrombosis [8].
  • Thus, when judiciously combined with anti-androgens, WA inhibits survival of both androgen-responsive and androgen-refractory prostate cancer cells by a Par-4-dependent mechanism [4].
  • Prostate apoptosis response-4 (Par-4), a protein containing a leucine zipper domain within a death domain, is up-regulated in prostate cancer cells and hippocampal neurons induced to undergo apoptosis [9].

Biological context of F2rl3

  • Down-regulation of PAR4 expression in microglial cultures by a specific antisense, but not a sense, oligonucleotide reduced PAR4AP-induced TNF-alpha [10].
  • We conclude that plasmin induces platelet aggregation primarily through slow cleavage of PAR-4 [11].
  • Further, the phenotype of mice reconstituted with Par4-/- marrow was almost as dramatic as that seen in Nf-e2-/- mice, which lack platelets [12].
  • However, in addition to its role in platelets, PAR4 contributes to thrombin signaling in cells in the blood vessel wall that might participate in hemostasis and thrombosis, such as endothelial cells [12].
  • We show that in tumors formed after engraftment of EBCs into mouse brain, expression of the pluripotency marker Oct-4 colocalized with that of prostate apoptosis response-4 (PAR-4), a protein mediating ceramide-induced apoptosis during neural differentiation of ES cells [13].

Anatomical context of F2rl3


Associations of F2rl3 with chemical compounds


Regulatory relationships of F2rl3

  • Despite wild-type levels of alphaIIbbeta3, caspase-12(-/-) platelets exhibit reduced fibrinogen binding to alphaIIbbeta3 following stimulation by adenosine diphosphate (ADP) or protease-activated receptor 4 (PAR4) receptor-activating peptide [21].

Other interactions of F2rl3

  • We now report that mice that lacked both PAR4 and fibrinogen exsanguinated at birth like prothrombin-deficient mice [22].

Analytical, diagnostic and therapeutic context of F2rl3

  • One of the compounds, withaferin A (WA), a major constituent of the dietary compound Withania somnifera, induced Par-4-dependent apoptosis in androgen-refractory prostate cancer cells and regression of PC-3 xenografts in nude mice [4].
  • In sections of day E14.5 mouse brain, the intermediate zone showed intensive staining for complex gangliosides, but only low staining for apoptosis (TUNEL) and PAR-4 [23].
  • The current data suggest that early up-regulation of Par-4 plays a pivotal role in ischemic neuronal death in animal models of stroke and cardiac arrest [18].
  • After transient focal ischemia in mice, Par-4 levels were increased 6 to 12 hours after reperfusion in the infarcted cortex and the striatum, and activation of caspase-8 occurred with a similar time course [18].
  • The expression of prostate apoptotic response-4 (Par-4) was detected by Western blot [24].


  1. Role of thrombin signalling in platelets in haemostasis and thrombosis. Sambrano, G.R., Weiss, E.J., Zheng, Y.W., Huang, W., Coughlin, S.R. Nature (2001) [Pubmed]
  2. Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Camerer, E., Qazi, A.A., Duong, D.N., Cornelissen, I., Advincula, R., Coughlin, S.R. Blood (2004) [Pubmed]
  3. Roles of protease-activated receptors in a mouse model of endotoxemia. Camerer, E., Cornelissen, I., Kataoka, H., Duong, D.N., Zheng, Y.W., Coughlin, S.R. Blood (2006) [Pubmed]
  4. Par-4-dependent apoptosis by the dietary compound withaferin a in prostate cancer cells. Srinivasan, S., Ranga, R.S., Burikhanov, R., Han, S.S., Chendil, D. Cancer Res. (2007) [Pubmed]
  5. Par-4 links dopamine signaling and depression. Park, S.K., Nguyen, M.D., Fischer, A., Luke, M.P., Affar, e.l. .B., Dieffenbach, P.B., Tseng, H.C., Shi, Y., Tsai, L.H. Cell (2005) [Pubmed]
  6. The thrombomodulin-protein C system is essential for the maintenance of pregnancy. Isermann, B., Sood, R., Pawlinski, R., Zogg, M., Kalloway, S., Degen, J.L., Mackman, N., Weiler, H. Nat. Med. (2003) [Pubmed]
  7. Regulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramide. Bieberich, E., MacKinnon, S., Silva, J., Noggle, S., Condie, B.G. J. Cell Biol. (2003) [Pubmed]
  8. Protection against thrombosis in mice lacking PAR3. Weiss, E.J., Hamilton, J.R., Lease, K.E., Coughlin, S.R. Blood (2002) [Pubmed]
  9. The prostate apoptosis response-4 protein participates in motor neuron degeneration in amyotrophic lateral sclerosis. Pedersen, W.A., Luo, H., Kruman, I., Kasarskis, E., Mattson, M.P. FASEB J. (2000) [Pubmed]
  10. Persistent protease-activated receptor 4 signaling mediates thrombin-induced microglial activation. Suo, Z., Wu, M., Citron, B.A., Gao, C., Festoff, B.W. J. Biol. Chem. (2003) [Pubmed]
  11. Plasmin-mediated activation of platelets occurs by cleavage of protease-activated receptor 4. Quinton, T.M., Kim, S., Derian, C.K., Jin, J., Kunapuli, S.P. J. Biol. Chem. (2004) [Pubmed]
  12. Impaired hemostasis and protection against thrombosis in protease-activated receptor 4-deficient mice is due to lack of thrombin signaling in platelets. Hamilton, J.R., Cornelissen, I., Coughlin, S.R. J. Thromb. Haemost. (2004) [Pubmed]
  13. Selective apoptosis of pluripotent mouse and human stem cells by novel ceramide analogues prevents teratoma formation and enriches for neural precursors in ES cell-derived neural transplants. Bieberich, E., Silva, J., Wang, G., Krishnamurthy, K., Condie, B.G. J. Cell Biol. (2004) [Pubmed]
  14. Genetic evidence that protease-activated receptors mediate factor Xa signaling in endothelial cells. Camerer, E., Kataoka, H., Kahn, M., Lease, K., Coughlin, S.R. J. Biol. Chem. (2002) [Pubmed]
  15. Studies on the receptors mediating responses of osteoblasts to thrombin. Song, S.J., Pagel, C.N., Pike, R.N., Mackie, E.J. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  16. Targeted ablation of Par-4 reveals a cell type-specific susceptibility to apoptosis-inducing agents. Affar, e.l. .B., Luke, M.P., Gay, F., Calvo, D., Sui, G., Weiss, R.S., Li, E., Shi, Y. Cancer Res. (2006) [Pubmed]
  17. Participation of prostate apoptosis response-4 in degeneration of dopaminergic neurons in models of Parkinson's disease. Duan, W., Zhang, Z., Gash, D.M., Mattson, M.P. Ann. Neurol. (1999) [Pubmed]
  18. Evidence for the involvement of Par-4 in ischemic neuron cell death. Culmsee, C., Zhu, Y., Krieglstein, J., Mattson, M.P. J. Cereb. Blood Flow Metab. (2001) [Pubmed]
  19. Long-term melatonin or 17beta-estradiol supplementation alleviates oxidative stress in ovariectomized adult rats. Feng, Z., Zhang, J.T. Free Radic. Biol. Med. (2005) [Pubmed]
  20. Do heterotrimeric G proteins redistribute upon G protein-coupled receptor stimulation in platelets? Kahner, B.N., Quinton, T.M., Langan, S., Kunapuli, S.P. Platelets (2006) [Pubmed]
  21. Caspase-12: a developmental link between G-protein-coupled receptors and integrin alphaIIbbeta3 activation. Kerrigan, S.W., Gaur, M., Murphy, R.P., Shattil, S.J., Leavitt, A.D. Blood (2004) [Pubmed]
  22. Combined deficiency of protease-activated receptor-4 and fibrinogen recapitulates the hemostatic defect but not the embryonic lethality of prothrombin deficiency. Camerer, E., Duong, D.N., Hamilton, J.R., Coughlin, S.R. Blood (2004) [Pubmed]
  23. Regulation of apoptosis during neuronal differentiation by ceramide and b-series complex gangliosides. Bieberich, E., MacKinnon, S., Silva, J., Yu, R.K. J. Biol. Chem. (2001) [Pubmed]
  24. Prostate apoptosis response-4 involved in the protective effect of salvianolic acid B against amyloid beta peptide-induced damage in PC12 cells. Tang, M., Zhang, J. Jpn. J. Pharmacol. (2002) [Pubmed]
WikiGenes - Universities