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Gene Review

LPAR3  -  lysophosphatidic acid receptor 3

Homo sapiens

Synonyms: EDG7, Edg-7, GPCR, HOFNH30, LP-A3, ...
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Disease relevance of EDG7

  • Neither the EDG7- nor EDG4-transduced Ca(2+) response or cAMP accumulation was inhibited by pertussis toxin [1].
  • Edg4 and Edg7 levels are consistently increased in malignant ovarian epithelial cells contributing to the aberrant response of ovarian cancer cells to LPA [2].
  • Northern blot analysis revealed that various gastric cancer cells expressed variable levels of LPA1, LPA2, and LPA3 without a consistent pattern [3].
  • The results of these studies suggest that RRV ORF74 encodes a GPCR with properties similar to those of its homologue in HHV-8 and that this gene may play a role in RRV-associated pathogenesis [4].
  • In a rat hepatoma Rh7777 cell line that lacks endogenous responses to lysophosphatidic acid, this lipid mediator, but not others, evokes calcium transients when the cells have been transfected with Edg-7 or Edg-4 DNAs [5].

Psychiatry related information on EDG7

  • Given the complexity of neurological disorders such as ischemic stroke, Alzheimer's disease and epilepsy, exploitation mGlu receptor-associated GPCR interactions may prove efficacious in the treatment of such disorders [6].

High impact information on EDG7

  • Future high-resolution structural studies of rhodopsin and other GPCRs will form a basis to elucidate the detailed molecular mechanism of GPCR-mediated signal transduction [7].
  • Significantly, GPCR-containing CCPs are also functionally distinct, as their surface residence time is regulated locally by GPCR cargo via PDZ-dependent linkage to the actin cytoskeleton [8].
  • Our results reveal a novel function of betaarr1 as a cytoplasm-nucleus messenger in GPCR signaling and elucidate an epigenetic mechanism for direct GPCR signaling from cell membrane to the nucleus through signal-dependent histone modification [9].
  • (2005) provide evidence that beta-arrestin 1 moves to the nucleus in response to GPCR stimulation, where it regulates gene expression by facilitating histone acetylation at specific gene promoters [10].
  • A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription [9].

Chemical compound and disease context of EDG7


Biological context of EDG7


Anatomical context of EDG7


Associations of EDG7 with chemical compounds


Physical interactions of EDG7

  • There is increasing evidence that LPA signaling reprograms gene expression, but the GPCR-induced pathways connecting LPA receptor stimulation to downstream transcription factors are not well characterized [23].

Regulatory relationships of EDG7


Other interactions of EDG7


Analytical, diagnostic and therapeutic context of EDG7

  • RT-PCR analysis demonstrated that HOFNH30 mRNA is expressed in placenta whereas EDG7 mRNA shows highest expression in prostate [28].
  • Graded reductions in GPCR expression can be achieved through antisense strategies or total gene ablation or replacement can be achieved through gene targeting strategies, and exogenous expression of wild-type or mutant GPCR isoforms can be accomplished with transgenic technologies [29].
  • Techniques: GPCR assembly, pharmacology and screening by flow cytometry [30].
  • In the present study we demonstrate the formation of an agonist-induced multimeric complex containing a GPCR, betaarrestin 2, and the beta2-adaptin subunit of AP-2. beta2-Adaptin binds betaarrestin 2 in a yeast two-hybrid assay and coimmunoprecipitates with betaarrestins and beta2AR in an agonist-dependent manner in HEK-293 cells [31].
  • In addition, Rho is the only GPCR for which the presumed higher-order oligomeric state has been demonstrated, by imaging native disk membranes using atomic force microscopy (AFM) [32].


  1. Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid. Bandoh, K., Aoki, J., Hosono, H., Kobayashi, S., Kobayashi, T., Murakami-Murofushi, K., Tsujimoto, M., Arai, H., Inoue, K. J. Biol. Chem. (1999) [Pubmed]
  2. Critical role of lysophospholipids in the pathophysiology, diagnosis, and management of ovarian cancer. Mills, G.B., Eder, A., Fang, X., Hasegawa, Y., Mao, M., Lu, Y., Tanyi, J., Tabassam, F.H., Wiener, J., Lapushin, R., Yu, S., Parrott, J.A., Compton, T., Tribley, W., Fishman, D., Stack, M.S., Gaudette, D., Jaffe, R., Furui, T., Aoki, J., Erickson, J.R. Cancer Treat. Res. (2002) [Pubmed]
  3. Dual mode regulation of migration by lysophosphatidic acid in human gastric cancer cells. Shida, D., Kitayama, J., Yamaguchi, H., Hama, K., Aoki, J., Arai, H., Yamashita, H., Mori, K., Sako, A., Konishi, T., Watanabe, T., Sakai, T., Suzuki, R., Ohta, H., Takuwa, Y., Nagawa, H. Exp. Cell Res. (2004) [Pubmed]
  4. A G protein-coupled receptor encoded by rhesus rhadinovirus is similar to ORF74 of Kaposi's sarcoma-associated herpesvirus. Estep, R.D., Axthelm, M.K., Wong, S.W. J. Virol. (2003) [Pubmed]
  5. Molecular cloning and characterization of a lysophosphatidic acid receptor, Edg-7, expressed in prostate. Im, D.S., Heise, C.E., Harding, M.A., George, S.R., O'Dowd, B.F., Theodorescu, D., Lynch, K.R. Mol. Pharmacol. (2000) [Pubmed]
  6. Emerging signalling and protein interactions mediated via metabotropic glutamate receptors. Moldrich, R.X., Beart, P.M. Current drug targets. CNS and neurological disorders. (2003) [Pubmed]
  7. Rhodopsin: structural basis of molecular physiology. Menon, S.T., Han, M., Sakmar, T.P. Physiol. Rev. (2001) [Pubmed]
  8. Cargo regulates clathrin-coated pit dynamics. Puthenveedu, M.A., von Zastrow, M. Cell (2006) [Pubmed]
  9. A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. Kang, J., Shi, Y., Xiang, B., Qu, B., Su, W., Zhu, M., Zhang, M., Bao, G., Wang, F., Zhang, X., Yang, R., Fan, F., Chen, X., Pei, G., Ma, L. Cell (2005) [Pubmed]
  10. Beta-arrestin goes nuclear. Beaulieu, J.M., Caron, M.G. Cell (2005) [Pubmed]
  11. TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells. Gschwind, A., Hart, S., Fischer, O.M., Ullrich, A. EMBO J. (2003) [Pubmed]
  12. A central role of EGF receptor transactivation in angiotensin II -induced cardiac hypertrophy. Shah, B.H., Catt, K.J. Trends Pharmacol. Sci. (2003) [Pubmed]
  13. E-selectin permits communication between PAF receptors and TRPC channels in human neutrophils. McMeekin, S.R., Dransfield, I., Rossi, A.G., Haslett, C., Walker, T.R. Blood (2006) [Pubmed]
  14. Pleiotropic coupling of G protein-coupled receptors to the mitogen-activated protein kinase cascade. Role of focal adhesions and receptor tyrosine kinases. Della Rocca, G.J., Maudsley, S., Daaka, Y., Lefkowitz, R.J., Luttrell, L.M. J. Biol. Chem. (1999) [Pubmed]
  15. The synthetic peptide derived from the NH2-terminal extracellular region of an orphan G protein-coupled receptor, GPR1, preferentially inhibits infection of X4 HIV-1. Jinno-Oue, A., Shimizu, N., Soda, Y., Tanaka, A., Ohtsuki, T., Kurosaki, D., Suzuki, Y., Hoshino, H. J. Biol. Chem. (2005) [Pubmed]
  16. Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species. Structure-activity relationship of cloned LPA receptors. Bandoh, K., Aoki, J., Taira, A., Tsujimoto, M., Arai, H., Inoue, K. FEBS Lett. (2000) [Pubmed]
  17. Cell density-dependent expression of EDG family receptors and mesangial cell proliferation: role in lysophosphatidic acid-mediated cell growth. Xing, Y., Ganji, S.H., Noh, J.W., Kamanna, V.S. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  18. Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Lee, M.J., Thangada, S., Paik, J.H., Sapkota, G.P., Ancellin, N., Chae, S.S., Wu, M., Morales-Ruiz, M., Sessa, W.C., Alessi, D.R., Hla, T. Mol. Cell (2001) [Pubmed]
  19. Lysophosphatidic acid (LPA) receptors are activated differentially by biological fluids: possible role of LPA-binding proteins in activation of LPA receptors. Hama, K., Bandoh, K., Kakehi, Y., Aoki, J., Arai, H. FEBS Lett. (2002) [Pubmed]
  20. Dual mechanisms for lysophosphatidic acid stimulation of human ovarian carcinoma cells. Hu, Y.L., Albanese, C., Pestell, R.G., Jaffe, R.B. J. Natl. Cancer Inst. (2003) [Pubmed]
  21. Lysophosphatidic acid induces chemotaxis, oxygen radical production, CD11b up-regulation, Ca2+ mobilization, and actin reorganization in human eosinophils via pertussis toxin-sensitive G proteins. Idzko, M., Laut, M., Panther, E., Sorichter, S., Dürk, T., Fluhr, J.W., Herouy, Y., Mockenhaupt, M., Myrtek, D., Elsner, P., Norgauer, J. J. Immunol. (2004) [Pubmed]
  22. Activity of 2-substituted lysophosphatidic acid (LPA) analogs at LPA receptors: discovery of a LPA1/LPA3 receptor antagonist. Heise, C.E., Santos, W.L., Schreihofer, A.M., Heasley, B.H., Mukhin, Y.V., Macdonald, T.L., Lynch, K.R. Mol. Pharmacol. (2001) [Pubmed]
  23. Bcl10 and Malt1 control lysophosphatidic acid-induced NF-{kappa}B activation and cytokine production. Klemm, S., Zimmermann, S., Peschel, C., Mak, T.W., Ruland, J. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  24. Kaposi's sarcoma-associated herpesvirus-encoded G protein-coupled receptor activation of c-jun amino-terminal kinase/stress-activated protein kinase and lyn kinase is mediated by related adhesion focal tyrosine kinase/proline-rich tyrosine kinase 2. Munshi, N., Ganju, R.K., Avraham, S., Mesri, E.A., Groopman, J.E. J. Biol. Chem. (1999) [Pubmed]
  25. A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid. Sonoda, H., Aoki, J., Hiramatsu, T., Ishida, M., Bandoh, K., Nagai, Y., Taguchi, R., Inoue, K., Arai, H. J. Biol. Chem. (2002) [Pubmed]
  26. Glucagon-like peptide-1 synthetic analogs: new therapeutic agents for use in the treatment of diabetes mellitus. Holz, G.G., Chepurny, O.G. Current medicinal chemistry. (2003) [Pubmed]
  27. PTEN as an effector in the signaling of antimigratory G protein-coupled receptor. Sanchez, T., Thangada, S., Wu, M.T., Kontos, C.D., Wu, D., Wu, H., Hla, T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  28. Identification of an EDG7 variant, HOFNH30, a G-protein-coupled receptor for lysophosphatidic acid. Fitzgerald, L.R., Dytko, G.M., Sarau, H.M., Mannan, I.J., Ellis, C., Lane, P.A., Tan, K.B., Murdock, P.R., Wilson, S., Bergsma, D.J., Ames, R.S., Foley, J.J., Campbell, D.A., McMillan, L., Evans, N., Elshourbagy, N.A., Minehart, H., Tsui, P. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  29. G protein-coupled receptors: functional and mechanistic insights through altered gene expression. Rohrer, D.K., Kobilka, B.K. Physiol. Rev. (1998) [Pubmed]
  30. Techniques: GPCR assembly, pharmacology and screening by flow cytometry. Waller, A., Simons, P.C., Biggs, S.M., Edwards, B.S., Prossnitz, E.R., Sklar, L.A. Trends Pharmacol. Sci. (2004) [Pubmed]
  31. The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Laporte, S.A., Oakley, R.H., Zhang, J., Holt, J.A., Ferguson, S.S., Caron, M.G., Barak, L.S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  32. Structure of the rhodopsin dimer: a working model for G-protein-coupled receptors. Fotiadis, D., Jastrzebska, B., Philippsen, A., Müller, D.J., Palczewski, K., Engel, A. Curr. Opin. Struct. Biol. (2006) [Pubmed]
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