Recombinant Human Proteinase-activated receptor 4 (F2RL3)

1. Data suggested that PAR4-AP-induced platelet reactivity between PAR4 rs773902 was associated with altered intensity of Ca(2+) mobilization and ERK activation. PMID: 29289806
2. Thrombin binding to extra-cellular loop II (ECLII) of PAR4 is important for its cleavage and activation of PAR4. PMID: 28448853
3. PAR4 has a role in mediating platelet aggregation; its blockade provides antithrombotic activity PMID: 28053157
4. PAR4 is required for platelet procoagulant function during thrombus formation in human blood PMID: 26878340
5. Prospective study demonstrated that AHRR and F2RL3 methylation levels had inverse relationships with self-reported smoking status and accurately discriminated for both current- and former- smoking. Moreover, methylation markers distinguished former smokers from never-smokers with high accuracy and significantly associated with an increased risk of lung cancer. PMID: 28453567
6. F2RL3 variants have the potential to markedly alter platelet PAR4 reactivity particularly after exposure to therapeutic PAR1 antagonists. PMID: 26966273
7. these findings are the first to show that internalization of activated PAR4 is linked to proper ERK1/2 and Akt activation. PMID: 27402844
8. an intracellular PAR4 C-terminal motif that regulates calcium signaling and beta-arrestin interactions, was identified. PMID: 28126849
9. the contribution of PAR1 and PAR4 to thrombin-mediated activation of the platelet fibrin receptor (GPIIbIIIa), is reported. PMID: 27784794
10. Suppression of PAR4 expression has no significant effect on the proliferation of SW620 cells, but can inhibit the migration of the cells. PMID: 27126938
11. Both GPIbalpha and PAR4 are required for thrombin-induced reactive oxygen species formation in human platelets. PMID: 26569550
12. Bladder PAR activation elicits urothelial MIF release and urothelial MIF receptor signaling at least partly through CXCR4 to result in abdominal hypersensitivity without overt bladder inflammation PMID: 26020638
13. protease-activated receptor 4 and Trefoil factor 2 are expressed in human colorectal cancer PMID: 25876034
14. The PAR4 expression and activation via intracellular signaling pathways and the role of PAR4 signaling pathways in the development and maintenance of pain. PMID: 25664811
15. This review summarizes the roles of PAR4 in coagulation and other extracellular protease pathways. PMID: 25120239
16. Findings suggested that F2RL3 methylation is a very strong predictor of lung cancer risk and mortality, particularly at older age. PMID: 25821117
17. Lower F2RL3 methylation is a strong predictor of mortality, including all-cause, cardiovascular, cancer and other mortality. Systemic adverse effects of smoking may be mediated by pathways associated with F2RL3 methylation. PMID: 24510982
18. exosite II is critical for activation of PAR4. PMID: 24990072
19. provide evidence against the hypothesis that PAR-1 and PAR-4 stimulation of platelets trigger differential release of alpha-granules PMID: 24776597
20. Washed platelets from black volunteers were hyperaggregable in response to PAR4-mediated platelet stimulation compared with whites. PMID: 25278289
21. PAR-4 appears to play a hitherto unsuspected role in diabetic vasculopathy. PMID: 25239438
22. Quantitative trait locus analysis identified 3 common single nucleotide polymorphisms in the PAR4 gene (F2RL3) associated with PAR4-induced platelet aggregation. Thr120 was more common in blacks than whites. PMID: 25293779
23. PAR4-P2Y12 association supports arrestin-mediated sustained signaling to Akt. PMID: 24723492
24. PAR4 and GPVI-mediated platelet reactivity involves 12-lipoxygenase PMID: 23784669
25. Phosphatidylcholine transfer protein contributes to the racial difference in PAR4-mediated platelet activation. PMID: 24216752
26. The F2RL3 rs773857 risk allele homozygotes are associated with risk for increased platelet count and hyperactivity. PMID: 22228373
27. Stimulation of PAR4 on platelets leads to faster and more robust thrombin generation, compared to PAR-1 stimulation. PMID: 23307185
28. The results seem to indicate methylation in F2RL3 to be a potential mediator of the detrimental impact of smoking and mortality in coronary heart disease PMID: 22511653
29. PAR4 is down-regulated in the colonic mast cells of post-infectious irritable bowel syndrome. PMID: 22151913
30. Novel role for proteinase-activated receptor 2 (PAR2) in membrane trafficking of proteinase-activated receptor 4 (PAR4). PMID: 22411985
31. mutations that disrupted dimer formation had reduced calcium mobilization in response to the PAR4 agonist peptide. PMID: 22318735
32. PKC inhibition markedly enhances Ca2+ signaling and phosphatidylserine exposure downstream of protease-activated receptor-1 but not protease-activated receptor-4 in human platelets. PMID: 21649850
33. down-regulation of PAR4 expression occurs frequently in gastric cancers and exhibits association with more aggressive gastric cancer PMID: 21635966
34. The present study elucidates further differences in human platelet PAR signalling regulation and provides evidence for a cross-talk in which PAR4 signalling counteracts mechanisms involved in PAR1 signalling down-regulation. PMID: 21391917
35. High glucose enhances smooth muscle cell responsiveness to thrombin through transcriptional upregulation of PAR-4, mediated via PKC and NFkappaB. PMID: 21164077
36. Protease-activated receptor signaling in platelets activates cytosolic phospholipase A2alpha differently for cyclooxygenase-1 and 12-lipoxygenase catalysis. PMID: 21127289
37. Results suggest that lower levels of protease-activated receptors 1 and 4 contribute to the poor thrombin induced aggregation observed with newborn platelets, which can not be compensated by higher levels of GPIbalpha. PMID: 20807173
38. Low concentrations of alpha-thrombin accelerate tissue factor-induced thrombin generation on the surface of vascular smooth muscle cells, and this effect is mediated by PAR-3 and PAR-4. PMID: 20930172
39. Human cytomegalovirus induces PARs expression through transcriptional activation in endothelial cells, increasing sensitivity to thrombin. PMID: 20155436
40. SPSB1 and SPSB4 bind strongly to both Par-4 and VASA peptides. PMID: 20561531
41. Data show that PAR1 and PAR4-activating peptides were as effective as thrombin in inducing annexin V binding in combination with collagen-related peptide in diluted whole blood and platelet rich plasma, but not in washed platelets. PMID: 20230207
42. Thrombin enhances the migration of chondrosarcoma cells by increasing MMP-2 and MMP-13 expression through the PAR/PLC/PKCalpha/c-Src/NF-kappaB signal transduction pathway. PMID: 20175118
43. Complement protease MASP-1 activates human endothelial cells through PAR4 cleavage PMID: 19667088
44. When expressed in respiratory epithelial cells and cell lines, protease-activated receptor 4 (PAR4)induces the release of IL-6, IL-8, and PGE2. PMID: 11907122
45. Activation of platelets via the PAR4 pathway, by treatment with PAR4 agonist peptide AYPGKF, results in thrombin-induced thromboxane production by platelets. PMID: 12006403
46. The signal from PAR4 stabilizes platelet-platelet aggregate formation in the absence of P2Y12 activation by ADP. PMID: 12008957
47. PAR4 is activated independently of GPIbalpha and ADP PMID: 12871418
48. Important role in regulation of thromboxane formation in platelets responding to thrombin through prolonged elevation of [Ca(2+)](i) and activation of phospholipase A(2). Can be activated by relatively low concentrations of thrombin in human platelets. PMID: 12888878
49. Protease-activated receptor-4 exodomains utilize dual prolines and an anionic retention motif for thrombin recognition and cleavage. PMID: 13678420
50. PAR-1 and PAR-4 have roles in activating GPIb translocation into the cytoskeleton in platelets PMID: 14521606

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HGNC: 3540

OMIM: 602779

KEGG: hsa:9002

STRING: 9606.ENSP00000248076

UniGene: Hs.137574