LPAR1 explained

Lysophosphatidic acid receptor 1 also known as LPA₁ is a protein that in humans is encoded by the LPAR1 gene.^{[1] [2] [3]} LPA₁ is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).^[4]

Function

The integral membrane protein encoded by this gene is a lysophosphatidic acid (LPA) receptor from a group known as EDG receptors. These receptors are members of the G protein-coupled receptor superfamily. Utilized by LPA for cell signaling, EDG receptors mediate diverse biologic functions, including proliferation, platelet aggregation, smooth muscle contraction, inhibition of neuroblastoma cell differentiation, chemotaxis, and tumor cell invasion. Alternative splicing of this gene has been observed and two transcript variants have been described, each encoding identical proteins. An alternate translation start codon has been identified, which results in isoforms differing in the N-terminal extracellular tail. In addition, an alternate polyadenylation site has been reported.^[1]

Cancer

LPAR1 gene has been detected progressively overexpressed in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy.^[5] For this reason, this gene is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression.^[6]

Evolution

Paralogues^[7]

• LPAR2
• LPAR3
• S1PR1
• S1PR3
• S1PR5
• S1PR4
• S1PR2
• CNR1
• MC3R
• MC5R
• MC4R
• GPR12
• MC2R
• GPR6
• CNR2
• GPR3
• MC1R
• GPR119

See also

• Lysophospholipid receptor

Further reading

• An S, Goetzl EJ, Lee H . Signaling mechanisms and molecular characteristics of G protein-coupled receptors for lysophosphatidic acid and sphingosine 1-phosphate. . J. Cell. Biochem. Suppl. . 30–31 . 147–57 . 1999 . 9893266 .
• Contos JJ, Ishii I, Chun J . Lysophosphatidic acid receptors. . Mol. Pharmacol. . 58 . 6 . 1188–96 . 2001 . 11093753 . 10.1124/mol.58.6.1188. 6936621 .
• Moolenaar WH, Kranenburg O, Postma FR, Zondag GC . Lysophosphatidic acid: G-protein signalling and cellular responses. . Curr. Opin. Cell Biol. . 9 . 2 . 168–73 . 1997 . 9069262 . 10.1016/S0955-0674(97)80059-2 .
• Fukushima N, Kimura Y, Chun J . A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid. . Proc. Natl. Acad. Sci. U.S.A. . 95 . 11 . 6151–6 . 1998 . 9600933 . 27607 . 10.1073/pnas.95.11.6151 . 1998PNAS...95.6151F . free .
• An S, Bleu T, Zheng Y, Goetzl EJ . Recombinant human G protein-coupled lysophosphatidic acid receptors mediate intracellular calcium mobilization. . Mol. Pharmacol. . 54 . 5 . 881–8 . 1998 . 9804623 . 10.1124/mol.54.5.881. 37327084 .
• Cervera P, Tirard M, Barron S, etal . Immunohistological localization of the myelinating cell-specific receptor LP(A1). . Glia . 38 . 2 . 126–36 . 2002 . 11948806 . 10.1002/glia.10054 . 21222546 .
• Hama K, Bandoh K, Kakehi Y, etal . Lysophosphatidic acid (LPA) receptors are activated differentially by biological fluids: possible role of LPA-binding proteins in activation of LPA receptors. . FEBS Lett. . 523 . 1–3 . 187–92 . 2002 . 12123830 . 10.1016/S0014-5793(02)02976-9 . 44924895 . free .
• Van Leeuwen FN, Olivo C, Grivell S, etal . Rac activation by lysophosphatidic acid LPA1 receptors through the guanine nucleotide exchange factor Tiam1. . J. Biol. Chem. . 278 . 1 . 400–6 . 2003 . 12393875 . 10.1074/jbc.M210151200 . free . 2066/186398 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
• Murph MM, Scaccia LA, Volpicelli LA, Radhakrishna H . Agonist-induced endocytosis of lysophosphatidic acid-coupled LPA1/EDG-2 receptors via a dynamin2- and Rab5-dependent pathway. . J. Cell Sci. . 116 . Pt 10 . 1969–80 . 2004 . 12668728 . 10.1242/jcs.00397 . free .
• Shida D, Kitayama J, Yamaguchi H, etal . Lysophosphatidic acid (LPA) enhances the metastatic potential of human colon carcinoma DLD1 cells through LPA1. . Cancer Res. . 63 . 7 . 1706–11 . 2003 . 12670925 .
• Matsuda A, Suzuki Y, Honda G, etal . Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. . Oncogene . 22 . 21 . 3307–18 . 2003 . 12761501 . 10.1038/sj.onc.1206406 . free .
• Xu J, Lai YJ, Lin WC, Lin FT . TRIP6 enhances lysophosphatidic acid-induced cell migration by interacting with the lysophosphatidic acid 2 receptor. . J. Biol. Chem. . 279 . 11 . 10459–68 . 2004 . 14688263 . 10.1074/jbc.M311891200 . 3904432 . free .
• Komuro Y, Watanabe T, Kitayama J, etal . The Immunohistochemical expression of endothelial cell differentiation gene-2 receptor in human colorectal adenomas. . Hepatogastroenterology . 50 . 54 . 1770–3 . 2004 . 14696401 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Kaneider NC, Lindner J, Feistritzer C, etal . The immune modulator FTY720 targets sphingosine-kinase-dependent migration of human monocytes in response to amyloid beta-protein and its precursor. . FASEB J. . 18 . 11 . 1309–11 . 2005 . 15208267 . 10.1096/fj.03-1050fje . free . 22590944 .

External links

• Web site: Lysophospholipid Receptors: LPA₁ . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology .

Notes and References

1. Web site: Entrez Gene: LPAR1 Lysophosphatidic acid receptor 1 .
2. 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. . 135 . 4 . 1071–83 . November 1996 . 8922387 . 2133395 . 10.1083/jcb.135.4.1071.
3. An S, Dickens MA, Bleu T, Hallmark OG, Goetzl EJ . Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid . Biochem. Biophys. Res. Commun. . 231 . 3 . 619–22 . February 1997 . 9070858 . 10.1006/bbrc.1997.6150 .
4. Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, Lin ME, Teo ST, Park KE, Mosley AN, Chun J . January 2010 . LPA Receptors: Subtypes and Biological Actions . Annual Review of Pharmacology and Toxicology . 50 . 1 . 157–186 . 10.1146/annurev.pharmtox.010909.105753 . 20055701.
5. Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F . Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes. . J Cell Physiol . 230. 4 . 802–812 . April 2015 . 25205602 . 10.1002/jcp.24808. 11392/2066612 . 24986454 . free .
6. Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F . Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes. . J Cell Physiol . 230. 4 . 802–812 . April 2015 . 25205602 . 10.1002/jcp.24808. 11392/2066612 . 24986454 . free .
7. Web site: GeneCards®: The Human Gene Database .