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Gene Review

PTGER4  -  prostaglandin E receptor 4 (subtype EP4)

Homo sapiens

Synonyms: EP4, EP4R, PGE receptor EP4 subtype, PGE2 receptor EP4 subtype, PTGER2, ...
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Disease relevance of PTGER4


High impact information on PTGER4

  • This suggests that the neonatal drop in prostaglandin E2 that triggers ductal closure is sensed through the EP4 receptor [6].
  • In contrast, EP4 receptor mRNA is predominantly expressed in the glomerulus, where it may contribute to the regulation of glomerular hemodynamics and renin release [7].
  • The major PGE2 receptors on epithelial cells, EP2 and EP4, increase cAMP production, which promotes growth and inhibits apoptosis in some cell types [8].
  • The anabolic action of PGE2 in bone has been linked to an elevated level of cAMP, thereby implicating the EP2 and/or EP4 receptor subtypes in bone formation [9].
  • These results suggest that activation of EP4 induces bone remodeling in vivo and that EP4-selective drugs may be beneficial in humans with osteoporosis [10].

Chemical compound and disease context of PTGER4


Biological context of PTGER4


Anatomical context of PTGER4


Associations of PTGER4 with chemical compounds


Physical interactions of PTGER4


Regulatory relationships of PTGER4


Other interactions of PTGER4

  • The effects of PGE(2) and selective agonists for PGE(2) receptor subtypes (EP1, EP2, EP3, and EP4) were also studied [21].
  • Co-localization studies showed that the endothelial cells stained positive for EP1-EP4 and FP and that co-localization was seen for EP4 and c-kit [28].
  • Butaprost, a selective EP2 agonist, and ONO-AE1-329, a selective EP4 agonist, significantly inhibited IL-1alpha-induced MMP-3 production, although butaprost was less potent than ONO-AE-1-329 [29].
  • AH-23848B, an EP4 antagonist, antagonized the inhibitory effect of IL-1beta-elicited ICAM-1 expression by PGE2 [20].
  • In addition, agents that increased intracellular cAMP, as is typical of EP4 receptor signaling, markedly increased CD44 expression [11].

Analytical, diagnostic and therapeutic context of PTGER4


  1. Endothelin-1-induced prostaglandin E2-EP2, EP4 signaling regulates vascular endothelial growth factor production and ovarian carcinoma cell invasion. Spinella, F., Rosanò, L., Di Castro, V., Natali, P.G., Bagnato, A. J. Biol. Chem. (2004) [Pubmed]
  2. Seminal plasma promotes the expression of tumorigenic and angiogenic genes in cervical adenocarcinoma cells via the E-series prostanoid 4 receptor. Muller, M., Sales, K.J., Katz, A.A., Jabbour, H.N. Endocrinology (2006) [Pubmed]
  3. Roles of prostanoids in colon carcinogenesis and their potential targeting for cancer chemoprevention. Mutoh, M., Takahashi, M., Wakabayashi, K. Curr. Pharm. Des. (2006) [Pubmed]
  4. Implication of prostaglandin receptors in the accumulation of osteoprotegerin in human osteoblast cultures. Moreau, M., Boileau, C., Martel-Pelletier, J., Brunet, J., Laufer, S., Pelletier, J.P. J. Rheumatol. (2006) [Pubmed]
  5. Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses. Kleivi, K., Lind, G.E., Diep, C.B., Meling, G.I., Brandal, L.T., Nesland, J.M., Myklebost, O., Rognum, T.O., Giercksky, K.E., Skotheim, R.I., Lothe, R.A. Mol. Cancer (2007) [Pubmed]
  6. The prostaglandin receptor EP4 triggers remodelling of the cardiovascular system at birth. Nguyen, M., Camenisch, T., Snouwaert, J.N., Hicks, E., Coffman, T.M., Anderson, P.A., Malouf, N.N., Koller, B.H. Nature (1997) [Pubmed]
  7. G protein-coupled prostanoid receptors and the kidney. Breyer, M.D., Breyer, R.M. Annu. Rev. Physiol. (2001) [Pubmed]
  8. Inhibition of apoptosis in normal and transformed intestinal epithelial cells by cAMP through induction of inhibitor of apoptosis protein (IAP)-2. Nishihara, H., Kizaka-Kondoh, S., Insel, P.A., Eckmann, L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. An EP2 receptor-selective prostaglandin E2 agonist induces bone healing. Paralkar, V.M., Borovecki, F., Ke, H.Z., Cameron, K.O., Lefker, B., Grasser, W.A., Owen, T.A., Li, M., DaSilva-Jardine, P., Zhou, M., Dunn, R.L., Dumont, F., Korsmeyer, R., Krasney, P., Brown, T.A., Plowchalk, D., Vukicevic, S., Thompson, D.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  10. Stimulation of bone formation and prevention of bone loss by prostaglandin E EP4 receptor activation. Yoshida, K., Oida, H., Kobayashi, T., Maruyama, T., Tanaka, M., Katayama, T., Yamaguchi, K., Segi, E., Tsuboyama, T., Matsushita, M., Ito, K., Ito, Y., Sugimoto, Y., Ushikubi, F., Ohuchida, S., Kondo, K., Nakamura, T., Narumiya, S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  11. Autocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent invasion. Dohadwala, M., Batra, R.K., Luo, J., Lin, Y., Krysan, K., Pold, M., Sharma, S., Dubinett, S.M. J. Biol. Chem. (2002) [Pubmed]
  12. Host and Direct Antitumor Effects and Profound Reduction in Tumor Metastasis with Selective EP4 Receptor Antagonism. Yang, L., Huang, Y., Porta, R., Yanagisawa, K., Gonzalez, A., Segi, E., Johnson, D.H., Narumiya, S., Carbone, D.P. Cancer Res. (2006) [Pubmed]
  13. Expression of COX-2 and PGE synthase and synthesis of PGE(2)in endometrial adenocarcinoma: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors. Jabbour, H.N., Milne, S.A., Williams, A.R., Anderson, R.A., Boddy, S.C. Br. J. Cancer (2001) [Pubmed]
  14. Prostaglandin E2 downregulates interleukin-12 production through EP4 receptors in human monocytes stimulated with lipopolysaccharide from Actinobacillus actinomycetemcomitans and interferon-gamma. Iwasaki, K., Noguchi, K., Endo, H., Kondo, H., Ishikawa, I. Oral Microbiol. Immunol. (2003) [Pubmed]
  15. Role of EP2 and EP4 receptor-selective agonists of prostaglandin E(2) in acute and chronic kidney failure. Vukicevic, S., Simic, P., Borovecki, F., Grgurevic, L., Rogic, D., Orlic, I., Grasser, W.A., Thompson, D.D., Paralkar, V.M. Kidney Int. (2006) [Pubmed]
  16. Vascular endothelial growth factor induction by prostaglandin E2 in human airway smooth muscle cells is mediated by E prostanoid EP2/EP4 receptors and SP-1 transcription factor binding sites. Bradbury, D., Clarke, D., Seedhouse, C., Corbett, L., Stocks, J., Knox, A. J. Biol. Chem. (2005) [Pubmed]
  17. Cyclooxygenase-2 induction by bradykinin in human pulmonary artery smooth muscle cells is mediated by the cyclic AMP response element through a novel autocrine loop involving endogenous prostaglandin E2, E-prostanoid 2 (EP2), and EP4 receptors. Bradbury, D.A., Newton, R., Zhu, Y.M., El-Haroun, H., Corbett, L., Knox, A.J. J. Biol. Chem. (2003) [Pubmed]
  18. Changing expression of cyclooxygenases and prostaglandin receptor EP4 during development of the human ductus arteriosus. Rheinlaender, C., Weber, S.C., Sarioglu, N., Strauss, E., Obladen, M., Koehne, P. Pediatr. Res. (2006) [Pubmed]
  19. Detection of EP2, EP4, and FP receptors in human ciliary epithelial and ciliary muscle cells. Mukhopadhyay, P., Geoghegan, T.E., Patil, R.V., Bhattacherjee, P., Paterson, C.A. Biochem. Pharmacol. (1997) [Pubmed]
  20. Cyclooxygenase-2-dependent prostaglandin E2 down-regulates intercellular adhesion molecule-1 expression via EP2/EP4 receptors in interleukin-1beta-stimulated human gingival fibroblasts. Noguchi, K., Iwasaki, K., Shitashige, M., Endo, H., Kondo, H., Ishikawa, I. J. Dent. Res. (2000) [Pubmed]
  21. Prostaglandin E2 is an enhancer of interleukin-1beta-induced expression of membrane-associated prostaglandin E synthase in rheumatoid synovial fibroblasts. Kojima, F., Naraba, H., Sasaki, Y., Beppu, M., Aoki, H., Kawai, S. Arthritis Rheum. (2003) [Pubmed]
  22. Comparison of agonist-induced internalization of the human EP2 and EP4 prostaglandin receptors: role of the carboxyl terminus in EP4 receptor sequestration. Desai, S., April, H., Nwaneshiudu, C., Ashby, B. Mol. Pharmacol. (2000) [Pubmed]
  23. Activation of lipid metabolism contributes to interleukin-8 production during Chlamydia trachomatis infection of cervical epithelial cells. Fukuda, E.Y., Lad, S.P., Mikolon, D.P., Iacobelli-Martinez, M., Li, E. Infect. Immun. (2005) [Pubmed]
  24. Regulation of bone morphogenetic protein-2 expression by endogenous prostaglandin E2 in human mesenchymal stem cells. Arikawa, T., Omura, K., Morita, I. J. Cell. Physiol. (2004) [Pubmed]
  25. Effects of prostagladin E(2) on gel-forming mucin secretion in normal human nasal epithelial cells. Kook Kim, J., Hoon Kim, C., Kim, K., Jong Jang, H., Jik Kim, H., Yoon, J.H. Acta Otolaryngol. (2006) [Pubmed]
  26. Pathological function of prostaglandin E2 receptors in transitional cell carcinoma of the upper urinary tract. Miyata, Y., Ohba, K., Kanda, S., Nomata, K., Eguchi, J., Hayashi, T., Kanetake, H. Virchows Arch. (2006) [Pubmed]
  27. Role of PGE2 and EP Receptors in the Pathogenesis of Rheumatoid Arthritis and as a Novel Therapeutic Strategy. Akaogi, J., Nozaki, T., Satoh, M., Yamada, H. Endocrine, metabolic & immune disorders drug targets (2006) [Pubmed]
  28. Prostaglandin E2 and F2{alpha} receptors in the human Fallopian tube before and after mifepristone treatment. Wånggren, K., Lalitkumar, P.G., Stavreus-Evers, A., Ståbi, B., Gemzell-Danielsson, K. Mol. Hum. Reprod. (2006) [Pubmed]
  29. Cyclooxygenase-2-dependent prostaglandin (PG) E2 downregulates matrix metalloproteinase-3 production via EP2/EP4 subtypes of PGE2 receptors in human periodontal ligament cells stimulated with interleukin-1alpha. Yan, M., Noguchi, K., Ruwanpura, S.M., Ishikawa, I. J. Periodontol. (2005) [Pubmed]
  30. The structure of the prostaglandin EP4 receptor gene and related pseudogenes. Foord, S.M., Marks, B., Stolz, M., Bufflier, E., Fraser, N.J., Lee, M.G. Genomics (1996) [Pubmed]
  31. Sequestration and phosphorylation of the prostaglandin E2 EP4 receptor: dependence on the C-terminal tail. Slipetz, D., Buchanan, S., Mackereth, C., Brewer, N., Pellow, V., Hao, C., Adam, M., Abramovitz, M., Metters, K.M. Biochem. Pharmacol. (2001) [Pubmed]
  32. GW627368X ((N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetyl} benzene sulphonamide): a novel, potent and selective prostanoid EP4 receptor antagonist. Wilson, R.J., Giblin, G.M., Roomans, S., Rhodes, S.A., Cartwright, K.A., Shield, V.J., Brown, J., Wise, A., Chowdhury, J., Pritchard, S., Coote, J., Noel, L.S., Kenakin, T., Burns-Kurtis, C.L., Morrison, V., Gray, D.W., Giles, H. Br. J. Pharmacol. (2006) [Pubmed]
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