LPA2 receptor

Target id: 273

Nomenclature: LPA2 receptor

Family: Lysophospholipid (LPA) receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for LPA2 receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 351 19p12 LPAR2 lysophosphatidic acid receptor 2 6
Mouse 7 348 8 33.91 cM Lpar2 lysophosphatidic acid receptor 2 6
Rat 7 264 16p14 Lpar2 lysophosphatidic acid receptor 2
Previous and Unofficial Names
Edg4 | Pbx4 | pre-B-cell leukemia transcription factor 4 | endothelial differentiation gene 4, lysophosphatidic acid G-protein-coupled receptor 4
Database Links
Specialist databases
GPCRDB lpar2_human (Hs), lpar2_mouse (Mm)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
LPA

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
LPA Mm Full agonist 8.0 – 8.2 pEC50 1,14
pEC50 8.0 – 8.2 (EC50 1x10-8 – 6.8x10-9 M) [1,14]
2-oleoyl-LPA Hs Agonist 8.0 pEC50 3
pEC50 8.0 [3]
NAEPA Mm Full agonist 7.5 pEC50 14
pEC50 7.5 (EC50 3x10-8 M) [14]
LPA Hs Agonist 6.7 – 8.2 pEC50 12,19
pEC50 6.7 – 8.2 [12,19]
oleoyl-thiophosphate Mm Partial agonist 6.6 pEC50 10
pEC50 6.6 (EC50 2.44x10-7 M) [10]
dodecylphosphate Hs Full agonist 6.2 pEC50 21
pEC50 6.2 (EC50 7x10-7 M) [21]
dodecyl-thiophosphate Mm Partial agonist 6.0 pEC50 10
pEC50 6.0 (EC50 1x10-6 M) [10]
decyl dihydrogen phosphate Hs Full agonist 5.4 pEC50 21
pEC50 5.4 (EC50 3.7x10-6 M) [21]
farnesyl diphosphate Hs Agonist 5.7 pIC50 22
pIC50 5.7 [22]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
BrP-LPA Mm Antagonist 6.6 pKi 23
pKi 6.6 (Ki 2.45x10-7 M) [23]
Ki16425 Hs Antagonist 5.3 pKi 17
pKi 5.3 [17]
compound 15 [PMID: 18178086] Mm Antagonist 7.8 pIC50 4
pIC50 7.8 (IC50 1.7x10-8 M) [4]
farnesyl monophosphate N/A Antagonist 6.8 pIC50 22
pIC50 6.8 [22]
BrP-LPA Mm Antagonist 6.3 pIC50 23
pIC50 6.3 (IC50 4.68x10-7 M) [23]
AM966 Hs Antagonist 5.8 pIC50 20
pIC50 5.8 [20]
AM966 Mm Antagonist 4.6 pIC50 20
pIC50 4.6 [20]
View species-specific antagonist tables
Antagonist Comments
Virtual screening experiments have shown H2L5186303 to be a potent antagonist of LPA2 [11].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G12/G13 family
Adenylate cyclase inhibition
Phospholipase A2 stimulation
Comments:  Others include: Phosphatidylinositol-3-Kinase, RAS, Rho, MAP kinase activation. For a detailed review please see [5]
References:  13
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G12/G13 family
References: 
Tissue Distribution
Leukocytes, testis, prostate, spleen, thymus, and pancreas
Species:  Human
Technique:  Northern blot
References:  1
Kidney, uterus, testis, lung, stomach, spleen, thymus, postnatal brain, heart, embryonic brain, limb buds, craniofacial regions, and Rathke’s pouch.
Species:  Mouse
Technique:  Northern blot and in situ hybridisation
References:  9,15,18
Abdominal/thoracic aortic vascular smooth muscle cell.
Expression level:  High
Species:  Mouse
Technique:  qRT-PCR
References:  8
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Cell rounding
Species:  Rat
Tissue:  Neuroblastoma (B103 cell line)
Response measured:  Cell rounding
References:  13
Glycolysis
Species:  Human
Tissue:  Ovarian cancer (Caov-3 and OVCA-432 cell lines)
Response measured:  Altered generation of [3]H water from [3]H glucose.
References:  16
Facilitates DNA damage repair. γ-radiation upregulates LPA2 expression via NF-κB. Pharmacological inhibition of LPA2 delays DNA damage resolution.
Species:  Rat
Tissue:  Small intestine IEC-6 crypt cells.
Response measured:  Expression of Lpar2, DNA damage marker resolution.
References:  2
Physiological Consequences of Altering Gene Expression
No obvious phenotypes, but a decrease in PLC activation is observed
Species:  Mouse
Tissue: 
Technique:  Gene targeting:- replacement vector, deletion of half of exon 2
References:  7
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
D3Bwg0562etm1Roni|Lpar2tm1Jch D3Bwg0562etm1Roni/D3Bwg0562etm1Roni,Lpar2tm1Jch/Lpar2tm1Jch
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:106530  MGI:1858422  MP:0004753 abnormal miniature excitatory postsynaptic currents PMID: 19766573 
Lpar2tm1Jch Lpar2tm1Jch/Lpar2tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1858422  MP:0002169 no abnormal phenotype detected PMID: 12215548 

References

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1. An S, Bleu T, Hallmark OG, Goetzl EJ. (1998) Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. J. Biol. Chem.273 (14): 7906-10. [PMID:9525886]

2. Balogh A, Shimizu Y, Lee SC, Norman DD, Gangwar R, Bavaria M, Moon C, Shukla P, Rao R, Ray R et al.. (2015) The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair. Cell. Signal.27 (9): 1751-62. [PMID:26027517]

3. Bandoh K, Aoki J, Taira A, Tsujimoto M, Arai H, Inoue K. (2000) Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species. Structure-activity relationship of cloned LPA receptors. FEBS Lett.478 (1-2): 159-65. [PMID:10922489]

4. Beck HP, Kohn T, Rubenstein S, Hedberg C, Schwandner R, Hasslinger K, Dai K, Li C, Liang L, Wesche H et al.. (2008) Discovery of potent LPA2 (EDG4) antagonists as potential anticancer agents. Bioorg. Med. Chem. Lett.18 (3): 1037-41. [PMID:18178086]

5. Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, Lin ME, Teo ST, Park KE, Mosley AN, Chun J. (2010) LPA receptors: subtypes and biological actions. Annu. Rev. Pharmacol. Toxicol.50: 157-86. [PMID:20055701]

6. Contos JJ, Chun J. (2000) Genomic characterization of the lysophosphatidic acid receptor gene, lp(A2)/Edg4, and identification of a frameshift mutation in a previously characterized cDNA. Genomics64 (2): 155-69. [PMID:10729222]

7. Contos JJ, Fukushima N, Weiner JA, Kaushal D, Chun J. (2000) Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. Proc. Natl. Acad. Sci. U.S.A.97 (24): 13384-9. [PMID:11087877]

8. Dancs PT, Ruisanchez É, Balogh A, Panta CR, Miklós Z, Nüsing RM, Aoki J, Chun J, Offermanns S, Tigyi G et al.. (2017) LPA1 receptor-mediated thromboxane A2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction. FASEB J.,  [Epub ahead of print]. [PMID:28069828]

9. Diez-Roux G, Banfi S, Sultan M, Geffers L, Anand S, Rozado D, Magen A, Canidio E, Pagani M, Peluso I et al.. (2011) A high-resolution anatomical atlas of the transcriptome in the mouse embryo. PLoS Biol.9 (1): e1000582. [PMID:21267068]

10. Durgam GG, Virag T, Walker MD, Tsukahara R, Yasuda S, Liliom K, van Meeteren LA, Moolenaar WH, Wilke N, Siess W et al.. (2005) Synthesis, structure-activity relationships, and biological evaluation of fatty alcohol phosphates as lysophosphatidic acid receptor ligands, activators of PPARgamma, and inhibitors of autotaxin. J. Med. Chem.48 (15): 4919-30. [PMID:16033271]

11. Fells JI, Tsukahara R, Fujiwara Y, Liu J, Perygin DH, Osborne DA, Tigyi G, Parrill AL. (2008) Identification of non-lipid LPA3 antagonists by virtual screening. Bioorg. Med. Chem.16 (11): 6207-17. [PMID:18467108]

12. Im DS, Heise CE, Harding MA, George SR, O'Dowd BF, Theodorescu D, Lynch KR. (2000) Molecular cloning and characterization of a lysophosphatidic acid receptor, Edg-7, expressed in prostate. Mol. Pharmacol.57 (4): 753-9. [PMID:10727522]

13. Ishii I, Contos JJ, Fukushima N, Chun J. (2000) Functional comparisons of the lysophosphatidic acid receptors, LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7 in neuronal cell lines using a retrovirus expression system. Mol. Pharmacol.58 (5): 895-902. [PMID:11040035]

14. Kano K, Arima N, Ohgami M, Aoki J. (2008) LPA and its analogs-attractive tools for elucidation of LPA biology and drug development. Curr. Med. Chem.15 (21): 2122-31. [PMID:18781939]

15. McGiffert C, Contos JJ, Friedman B, Chun J. (2002) Embryonic brain expression analysis of lysophospholipid receptor genes suggests roles for s1p(1) in neurogenesis and s1p(1-3) in angiogenesis. FEBS Lett.531 (1): 103-8. [PMID:12401212]

16. Mukherjee A, Ma Y, Yuan F, Gong Y, Fang Z, Mohamed EM, Berrios E, Shao H, Fang X. (2015) Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells. Neoplasia17 (9): 723-34. [PMID:26476080]

17. 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 DS, Nochi H, Tamoto K, Tomura H, Okajima F. (2003) Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol. Pharmacol.64 (4): 994-1005. [PMID:14500756]

18. Ohuchi H, Hamada A, Matsuda H, Takagi A, Tanaka M, Aoki J, Arai H, Noji S. (2008) Expression patterns of the lysophospholipid receptor genes during mouse early development. Dev. Dyn.237 (11): 3280-94. [PMID:18924241]

19. Santos WL, Heasley BH, Jarosz R, Carter KM, Lynch KR, Macdonald TL. (2004) Synthesis and biological evaluation of phosphonic and thiophosphoric acid derivatives of lysophosphatidic acid. Bioorg. Med. Chem. Lett.14 (13): 3473-6. [PMID:15177455]

20. Swaney JS, Chapman C, Correa LD, Stebbins KJ, Bundey RA, Prodanovich PC, Fagan P, Baccei CS, Santini AM, Hutchinson JH et al.. (2010) A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br. J. Pharmacol.160 (7): 1699-713. [PMID:20649573]

21. Virag T, Elrod DB, Liliom K, Sardar VM, Parrill AL, Yokoyama K, Durgam G, Deng W, Miller DD, Tigyi G. (2003) Fatty alcohol phosphates are subtype-selective agonists and antagonists of lysophosphatidic acid receptors. Mol. Pharmacol.63 (5): 1032-42. [PMID:12695531]

22. Williams JR, Khandoga AL, Goyal P, Fells JI, Perygin DH, Siess W, Parrill AL, Tigyi G, Fujiwara Y. (2009) Unique ligand selectivity of the GPR92/LPA5 lysophosphatidate receptor indicates role in human platelet activation. J. Biol. Chem.284 (25): 17304-19. [PMID:19366702]

23. Zhang H, Xu X, Gajewiak J, Tsukahara R, Fujiwara Y, Liu J, Fells JI, Perygin D, Parrill AL, Tigyi G et al.. (2009) Dual activity lysophosphatidic acid receptor pan-antagonist/autotaxin inhibitor reduces breast cancer cell migration in vitro and causes tumor regression in vivo. Cancer Res.69 (13): 5441-9. [PMID:19509223]

Contributors

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How to cite this page

Aaron Frantz, Yun C. Yung, Jerold Chun.
Lysophospholipid (LPA) receptors: LPA2 receptor. Last modified on 13/03/2017. Accessed on 22/01/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=273.