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Gene Review

LPAR1  -  lysophosphatidic acid receptor 1

Homo sapiens

Synonyms: EDG2, GPR26, Gpcr26, LPA receptor 1, LPA-1, ...
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Disease relevance of EDG2


High impact information on EDG2

  • Both Edg2 and Edg4 were detected in ovarian cancer cells; however, only Edg2 was present in normal ovarian surface epithelial cells and IOSE-29 cells [5].
  • 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 [6].
  • Here we report that silencing of the type 1 LPA receptor (LPA(1)) in cancer cells blocks the production of tumor-derived cytokines that are potent activators of osteoclast-mediated bone destruction and significantly reduces the progression of osteolytic bone metastases [7].
  • Antagonists of the LPA receptor prevented platelet and endothelial cell activation by mildly oxidized LDL [8].
  • A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid [9].

Chemical compound and disease context of EDG2


Biological context of EDG2


Anatomical context of EDG2

  • Northern blots revealed that two edg4 mRNA transcripts of 1.8 and 8 kilobases are distributed very differently from edg2 mRNAs in adult human tissues and several cancer cell lines [14].
  • In this study, we investigated the agonist-induced endocytosis of the human LPA1 receptor, bearing an N-terminal FLAG epitope tag, in stably transfected HeLa cells [12].
  • Additionally, these data suggest that EDG-7 and EDG-2 LPA receptors play a diverse role as proliferative and antiproliferative, respectively, in mesangial cells [13].
  • It revealed a significant decrease in the expression of LPA1 protein in cancer tissues compared to normal mucosa in nine of 16 cases, and in the remaining seven cases the expression levels was much the same [15].
  • Normal epithelium expressed both LPA1 and LPA2 mRNA at similar levels [15].

Associations of EDG2 with chemical compounds

  • Other LPA receptors, EDG4 but not EDG2, transduced the Ca(2+) response by LPA when expressed in Sf9 cells [11].
  • Lysophosphatidic acid (LPA) enhances the metastatic potential of human colon carcinoma DLD1 cells through LPA1 [3].
  • Internalization was both dose dependent and LPA specific since neither lysophophatidylcholine nor sphingosine-1-phosphate induced LPA1 endocytosis [12].
  • Ki16425 inhibited LPA-induced guanosine 5'-O-(3-thio)triphosphate binding as well as LPA receptor binding to membrane fractions with a same pharmacological specificity as in intact cells [16].
  • One compound with a bulky hydrophobic group (VPC12249) was a dual LPA1/LPA3 competitive antagonist [17].

Physical interactions of EDG2

  • Although the possibility of a specific G-protein-coupled LPA receptor protein has been suggested, characterization of such a receptor is lacking [18].

Regulatory relationships of EDG2

  • In addition, both dynamin2 K44A and Rab5 S34N mildly inhibited LPA1-dependent activation of serum response factor [12].
  • FGFR4 GLY388 isotype suppresses motility of MDA-MB-231 breast cancer cells by EDG-2 gene repression [19].
  • Further investigations concentrating on cell signalling and motility revealed an abrogation of phosphatidylinositol-3-kinase-dependent LPA-induced Akt activation and cell migration due to downregulation of the LPA receptor Edg-2 in FGFR4 G388-expressing MDA-MB-231 cells [19].

Other interactions of EDG2


Analytical, diagnostic and therapeutic context of EDG2


  1. Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer. Schulte, K.M., Beyer, A., Köhrer, K., Oberhäuser, S., Röher, H.D. Int. J. Cancer (2001) [Pubmed]
  2. Lysophospholipid growth factors in the initiation, progression, metastases, and management of ovarian cancer. Fang, X., Gaudette, D., Furui, T., Mao, M., Estrella, V., Eder, A., Pustilnik, T., Sasagawa, T., Lapushin, R., Yu, S., Jaffe, R.B., Wiener, J.R., Erickson, J.R., Mills, G.B. Ann. N. Y. Acad. Sci. (2000) [Pubmed]
  3. Lysophosphatidic acid (LPA) enhances the metastatic potential of human colon carcinoma DLD1 cells through LPA1. Shida, D., Kitayama, J., Yamaguchi, H., Okaji, Y., Tsuno, N.H., Watanabe, T., Takuwa, Y., Nagawa, H. Cancer Res. (2003) [Pubmed]
  4. 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]
  5. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. Hu, Y.L., Tee, M.K., Goetzl, E.J., Auersperg, N., Mills, G.B., Ferrara, N., Jaffe, R.B. J. Natl. Cancer Inst. (2001) [Pubmed]
  6. 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]
  7. The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases. Boucharaba, A., Serre, C.M., Guglielmi, J., Bordet, J.C., Clézardin, P., Peyruchaud, O. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by mildly oxidized low density lipoprotein and accumulates in human atherosclerotic lesions. Siess, W., Zangl, K.J., Essler, M., Bauer, M., Brandl, R., Corrinth, C., Bittman, R., Tigyi, G., Aepfelbacher, M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid. Fukushima, N., Kimura, Y., Chun, J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  10. Effect of inoculation sequence and nutrients upon Streptococcus mutans BHT and Streptococcus mitior LPA-1 growing on human teeth in an artificial mouth. Donoghue, H.D., Hudson, D.E., Perrons, C.J., Dibdin, G.H., Rapson, G., Shellis, R.P., Wilson, C.M. J. Appl. Bacteriol. (1983) [Pubmed]
  11. 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]
  12. Agonist-induced endocytosis of lysophosphatidic acid-coupled LPA1/EDG-2 receptors via a dynamin2- and Rab5-dependent pathway. Murph, M.M., Scaccia, L.A., Volpicelli, L.A., Radhakrishna, H. J. Cell. Sci. (2003) [Pubmed]
  13. 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]
  14. Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. An, S., Bleu, T., Hallmark, O.G., Goetzl, E.J. J. Biol. Chem. (1998) [Pubmed]
  15. Aberrant expression of lysophosphatidic acid (LPA) receptors in human colorectal cancer. Shida, D., Watanabe, T., Aoki, J., Hama, K., Kitayama, J., Sonoda, H., Kishi, Y., Yamaguchi, H., Sasaki, S., Sako, A., Konishi, T., Arai, H., Nagawa, H. Lab. Invest. (2004) [Pubmed]
  16. Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Ohta, H., Sato, K., Murata, N., Damirin, A., Malchinkhuu, E., Kon, J., Kimura, T., Tobo, M., Yamazaki, Y., Watanabe, T., Yagi, M., Sato, M., Suzuki, R., Murooka, H., Sakai, T., Nishitoba, T., Im, D.S., Nochi, H., Tamoto, K., Tomura, H., Okajima, F. Mol. Pharmacol. (2003) [Pubmed]
  17. 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]
  18. Activation of protein kinase C by lysophosphatidic acid: dependence on composition of phospholipid vesicles. Sando, J.J., Chertihin, O.I. Biochem. J. (1996) [Pubmed]
  19. FGFR4 GLY388 isotype suppresses motility of MDA-MB-231 breast cancer cells by EDG-2 gene repression. Stadler, C.R., Knyazev, P., Bange, J., Ullrich, A. Cell. Signal. (2006) [Pubmed]
  20. Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family. Noguchi, K., Ishii, S., Shimizu, T. J. Biol. Chem. (2003) [Pubmed]
  21. Mitogenic action of LPA in prostate. Daaka, Y. Biochim. Biophys. Acta (2002) [Pubmed]
  22. Identification of a phosphothionate analogue of lysophosphatidic acid (LPA) as a selective agonist of the LPA3 receptor. Hasegawa, Y., Erickson, J.R., Goddard, G.J., Yu, S., Liu, S., Cheng, K.W., Eder, A., Bandoh, K., Aoki, J., Jarosz, R., Schrier, A.D., Lynch, K.R., Mills, G.B., Fang, X. J. Biol. Chem. (2003) [Pubmed]
  23. Neutrophil sphingosine 1-phosphate and lysophosphatidic acid receptors in pneumonia. Rahaman, M., Costello, R.W., Belmonte, K.E., Gendy, S.S., Walsh, M.T. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  24. The Immunohistochemical expression of endothelial cell differentiation gene-2 receptor in human colorectal adenomas. Komuro, Y., Watanabe, T., Kitayama, J., Yamaguchi, H., Tsuno, N., Nagawa, H. Hepatogastroenterology (2003) [Pubmed]
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