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

Mus musculus

Synonyms: Coagulation factor II receptor-like 3, PAR-4, PAR4, Par4, Proteinase-activated receptor 4, ...
 
 
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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].

References

  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]
 
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