Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Lysophosphatidic Acid Receptor

  • Nobuyuki FukushimaEmail author
  • Tsuyoshi Kado
  • Toshifumi Tsujiuchi
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101681


Historical Background

Lysophosphatidic acid (LPA) is a simple phospholipid consisting of a fatty acid linked to sn-1 or sn-2 and a phosphate at 2n-3 position of the glycerol backbone (Fig. 1). Historically, LPA was considered to be a metabolite of membrane phospholipids until 1989, when it was suggested to act as an intercellular signaling molecule that stimulates cell proliferation through heterotrimeric G protein activation (van Corven et al. 1989). In 1996, the first LPA receptor gene ( Lpar1) was isolated as a G protein-coupled receptor (GPCR) gene predominantly expressed in the ventricular zone of the developing cerebral cortex of mice (Hecht et al. 1996). The mouse Lpar1 gene was originally termed ventricular zone gene-1 ( vzg-1), and the most related gene showing the highest percentage amino acid identity was endothelial...
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This work was supported by KINDAI research funding KD02 (N.F. and T.T.) and KINDAI School of Science and Engineering funding RK-052 and RK-062 (N.F.). We apologize to all authors whose primary research papers could not be cited directly due to space limitations.


  1. Chrencik JE, Roth CB, Terakado M, Kurata H, Omi R, Kihara Y, et al. Crystal structure of antagonist bound human lysophosphatidic acid receptor 1. Cell. 2015;161(7):1633–43. Epub 2015/06/20PubMedPubMedCentralCrossRefGoogle Scholar
  2. Fukushima N, Ishii S, Tsujiuchi T, Kagawa N, Katoh K. Comparative analyses of lysophosphatidic acid receptor-mediated signaling. Cell Mol Life Sci. 2015;72(12):2377–94 .Epub 2015/03/04CrossRefPubMedGoogle Scholar
  3. Hata E, Sasaki N, Takeda A, Tohya K, Umemoto E, Akahoshi N, et al. Lysophosphatidic acid receptors LPA4 and LPA6 differentially promote lymphocyte transmigration across high endothelial venules in lymph nodes. Int Immunol. 2016;28(6):283–92. Epub 2015/12/31CrossRefPubMedGoogle Scholar
  4. Hecht JH, Weiner JA, Post SR, Chun J. Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. J Cell Biol. 1996;135(4):1071–83.CrossRefPubMedGoogle Scholar
  5. Ishii I, Fukushima N, Ye X, Chun J. Lysophospholipid receptors: signaling and biology. Annu Rev Biochemist. 2004;73:321–54.CrossRefGoogle Scholar
  6. Kihara Y, Maceyka M, Spiegel S, Chun J. Lysophospholipid receptor nomenclature review: IUPHAR Review 8. Br J Pharmacol. 2014;171:3575–94.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Lee MJ, Van Brocklyn JR, Thangada S, Liu CH, Hand AR, Menzeleev R, et al. Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science. 1998;279(5356):1552–5.CrossRefPubMedGoogle Scholar
  8. Lee CW, Rivera R, Gardell S, Dubin AE, Chun J. GPR92 as a new G12/13 and Gq coupled lysophosphatidic acid receptor that increases cAMP: LPA5. J Biol Chem. 2006;281:23589–97.CrossRefPubMedGoogle Scholar
  9. Li G, Mosier PD, Fang X, Zhang Y. Toward the three-dimensional structure and lysophosphatidic acid binding characteristics of the LPA(4)/p2y(9)/GPR23 receptor: a homology modeling study. J Mol Graph Model. 2009;28(1):70–9. Epub 2009/05/09PubMedPubMedCentralCrossRefGoogle Scholar
  10. Noguchi K, Ishii S, Shimizu T. Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family. J Biol Chem. 2003;278(28):25600–6.CrossRefPubMedGoogle Scholar
  11. Oh DY, Yoon JM, Moon MJ, Hwang JI, Choe H, Lee JY, et al. Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92. J Biol Chem. 2008;283(30):21054–64. Epub 2008/05/24PubMedPubMedCentralCrossRefGoogle Scholar
  12. Pasternack SM, von Kugelgen I, Al Aboud K, Lee YA, Ruschendorf F, Voss K, et al. G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth. Nat Genet. 2008;40(3):329–34. Epub 2008/02/26CrossRefPubMedGoogle Scholar
  13. Raza SI, Muhammad D, Jan A, Ali RH, Hassan M, Ahmad W, et al. In silico analysis of missense mutations in LPAR6 reveals abnormal phospholipid signaling pathway leading to hypotrichosis. PLoS ONE. 2014;9:e104756.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Trimbuch T, Beed P, Vogt J, Schuchmann S, Maier N, Kintscher M, et al. Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling. Cell. 2009;138(6):1222–35.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Tsujiuchi T, Hirane M, Dong Y, Fukushima N. Diverse effects of LPA receptors on cell motile activities of cancer cells. J Recept Signal Transduct Res. 2014;34(3):149–53. Epub 2014/01/28CrossRefPubMedGoogle Scholar
  16. Valentine WJ, Fells JI, Perygin DH, Mujahid S, Yokoyama K, Fujiwara Y, et al. Subtype-specific residues involved in ligand activation of the endothelial differentiation gene family lysophosphatidic acid receptors. J Biol Chem. 2008;283(18):12175–87. Epub 2008/03/05PubMedPubMedCentralCrossRefGoogle Scholar
  17. van Corven EJ, Groenink A, Jalink K, Eichholtz T, Moolenaar WH. Lysophosphatidate-induced cell proliferation: identification and dissection of signaling pathways mediated by G proteins. Cell. 1989;59(1):45–54.CrossRefPubMedGoogle Scholar
  18. Williams JR, Khandoga AL, Goyal P, Fells JI, Perygin DH, Siess W, et al. Unique ligand selectivity of the GPR92/LPA5 lysophosphatidate receptor indicates role in human platelet activation. J Biol Chem. 2009;284(25):17304–19. Epub 2009/04/16PubMedPubMedCentralCrossRefGoogle Scholar
  19. Yanagida K, Masago K, Nakanishi H, Kihara Y, Hamano F, Tajima Y, et al. Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6. J Biol Chem. 2009;284(26):17731–41.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Yung YC, Stoddard NC, Chun J. LPA receptor signaling: pharmacology, physiology, and pathophysiology. J Lipid Res. 2014;55(7):1192–214. Epub 2014/03/20PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Nobuyuki Fukushima
    • 1
    Email author
  • Tsuyoshi Kado
    • 1
  • Toshifumi Tsujiuchi
    • 2
  1. 1.Division of Molecular Neurobiology, Department of Life ScienceKindai UniversityHigashiosakaJapan
  2. 2.Division of Molecular Oncology, Department of Life ScienceKindai UniversityHigashiosakaJapan