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LPA1 receptor

Family: Lysophospholipid (LPA) receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 364 9q31.3 LPAR1 lysophosphatidic acid receptor 1
Mouse 7 364 4 B3 Lpar1 lysophosphatidic acid receptor 1
Rat 7 364 5q24 Lpar1 lysophosphatidic acid receptor 1
Previous and Unofficial Names
EDG2
VZG1
LPA1
GPR26
edg-2
vzg-1
Gpcr26
Mrec1.3
rec0.1.3
VZG-1
Edg2
lp A1
rec.1.3
endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 2
Kdt2
Lpar1
MGC105279
LPA receptor 1
LPA-1
lysophosphatidic acid receptor 1
lysophosphatidic acid receptor Edg-2
AI326300
Database Links
ChEMBL Target 10808 (Hs), 100435 (Rn)
Ensembl ENSG00000198121 (Hs), ENSMUSG00000038668 (Mm), ENSRNOG00000013656 (Rn)
Entrez Gene 1902 (Hs), 14745 (Mm), 116744 (Rn)
GeneCards LPAR1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Lpar1 (Mm)
HomoloGene 1072 (Hs)
Human Protein Reference Database 03790 (Hs)
InterPro Q92633 (Hs), P61793 (Mm), P61794 (Rn)
KEGG Gene hsa:1902 (Hs), mmu:14745 (Mm), rno:116744 (Rn)
OMIM 602282 (Hs)
PharmGKB Gene PA162394187 (Hs)
PhosphoSitePlus Q92633 (Hs), P61793 (Mm), P61794 (Rn)
Protein Ontology (PRO) PRO:000001684 (Hs)
RefSeq Nucleotide NM_001401 (Hs), NM_010336 (Mm), NM_053936 (Rn)
RefSeq Protein NP_001392 (Hs), NP_034466 (Mm), NP_446388 (Rn)
TreeFam ENSG00000198121 (Hs), ENSMUSG00000038668 (Mm), ENSRNOG00000013656 (Rn)
UniGene Hs. 126667 (Hs)
UniProt Q92633 (Hs), P61793 (Mm), P61794 (Rn)
Wikipedia LPA1 receptor
Lysophospholipid (LPA) receptors
Search for 3D structures on the PDB
Search by keyword: Lysophospholipid (LPA) receptors LPA1 receptor Search by accession number: P61794, Q92633, P61793
Natural/Endogenous Ligand(s)
LPA
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
LPA Mm Agonist 8.23 pEC50 8
2-oleoyl-LPA Hs Agonist 6.7 pEC50 2
alkyl OMPT Hs Agonist 6.1 pEC50 11
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
VPC32183 Hs Antagonist 7.75 pKi 7
VPC12249 Hs Antagonist 6.86 pKi 9
Ki16425 Hs Antagonist 6.6 pKi 10
Ki16425 Mm Antagonist 6.6 pKi 10
dioctanoy​lglycerol​ pyrophos​phate Hs Antagonist 5.18 pKi 6
AM966 Mm Antagonist 7.7 pEC50 12
AM966 Hs Antagonist 7.8 pIC50 12
VPC32183 Hs Antagonist 6.96 pIC50 7
View species-specific antagonist tables
Antagonist Comments
Although we have recorded the in vitro, pIC50 for AM966 from the LPA-stimulated intracellular calcium release from CHO cells expressing hLPA1 receptors the same paper also reports the it inhibited LPA-induced chemotaxis (pIC50= 6.7) of human IMR-90 lung fibroblasts [12]
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G12/G13 family 		Adenylate cyclase inhibition
Phospholipase C stimulation
Other - See Comments
Comments:  In general LPA1 is known to induce many responses incliding cell proliferation and survival, cell migration, and cytoskeletal changes; altered cell-cell contact through serum-response element activation, Ca2+ mobilization, and adenylyl cyclase inhibition; and activation of mitogen-activated protein kinase, phospholipase C, Akt, and Rho pathways For a detailed review please see [3]
References: 
Tissue Distribution
embryonic cerebral dorsal telencephalon (cortical ventricular zone (VZ))
Expression level:  High
Species:  Mouse
Technique:  In situ hybridisation and RT-PCR, Western Blot
References:  5,8
brain, heart, lung, and testis
Expression level:  High
Species:  Mouse
Technique:  Northern blot
References:  13
kidney,spleen, thymus (not in liver)
Expression level:  Low
Species:  Mouse
Technique:  Northern Blot
References:  13
(postnatal murine nervous system) oligodendrocytes and Schwann cells, the myelinating cells of the central and peripheral nervous systems
Species:  Rat
Technique:  In situ hybridisation, histochemistry, immunocytochemistry, northern blot
References:  1
Expression Datasets

Click here to show/hide data

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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Physiological Consequences of Altering Gene Expression
Phenotypes include: (50 %) neonatal lethality; impaired suckling in neonatal pups; smaller size pups; craniofacial dysmorphism; increased apoptosis. Alterations in signaling characteristics are also observed.
Species:  Mouse
Tissue: 
Technique:  Gene knockout
References:  4
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0005332 abnormal amino acid level PMID: 14697676 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0000428 abnormal craniofacial morphology PMID: 14697676 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0001106 abnormal Schwann cell morphology PMID: 11087877 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0002651 abnormal sciatic nerve PMID: 11087877 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0005322 abnormal serotonin concentration PMID: 14697676 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0001436 abnormal suckling behavior PMID: 11087877 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0001255 decreased body height PMID: 14697676 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0006086 decreased body mass index PMID: 14697676 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0001265 decreased body size PMID: 11087877 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0009142 decreased prepulse inhibition PMID: 14697676 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0001107 decreased Schwann cell number PMID: 11087877 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0010025 decreased total body fat amount PMID: 11087877 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0000914 exencephaly PMID: 11087877 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0001914 hemorrhage PMID: 11087877 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0001402 hypoactivity PMID: 14697676 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0001906 increased dopamine level PMID: 14697676 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0004831 long incisors PMID: 14697676 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0002058 neonatal lethality PMID: 11087877 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0001300 ocular hypertelorism PMID: 11087877 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0001300 ocular hypertelorism PMID: 14697676 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0002081 perinatal lethality PMID: 14697676 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0001732 postnatal growth retardation PMID: 11087877 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0002082 postnatal lethality PMID: 11087877 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0002082 postnatal lethality PMID: 14697676 
Lpar1tm1Jch Lpar1tm1Jch/Lpar1tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:108429  MP:0000445 short snout PMID: 11087877 
Lpar1tm1Mcox Lpar1tm1Mcox/Lpar1tm1Mcox
B6.129P2-Lpar1		 MGI:108429  MP:0000445 short snout PMID: 14697676 

REFERENCES

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1. Allard, J; Barrón, S; Diaz, J; Lubetzki, C; Zalc, B; Schwartz, JC; Sokoloff, P. (1998) A rat G protein-coupled receptor selectively expressed in myelin-forming cells. Eur. J. Neurosci., 10 (3): 1045-53. [PMID:9753172]

2. 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]

3. 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]

4. 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]

5. Dubin, AE; Bahnson, T; Weiner, JA; Fukushima, N; Chun, J. (1999) Lysophosphatidic acid stimulates neurotransmitter-like conductance changes that precede GABA and L-glutamate in early, presumptive cortical neuroblasts. J. Neurosci., 19 (4): 1371-81. [PMID:9952414]

6. Fischer, DJ; Nusser, N; Virag, T; Yokoyama, K; Wang Da; Baker, DL; Bautista, D; Parrill, AL; Tigyi, G. (2001) Short-chain phosphatidates are subtype-selective antagonists of lysophosphatidic acid receptors. Mol. Pharmacol., 60 (4): 776-84. [PMID:11562440]

7. Heasley, BH; Jarosz, R; Lynch, KR; Macdonald, TL. (2004) Initial structure-activity relationships of lysophosphatidic acid receptor antagonists: discovery of a high-affinity LPA1/LPA3 receptor antagonist. Bioorg. Med. Chem. Lett., 14 (11): 2735-40. [PMID:15125924]

8. Hecht, JH; Weiner, JA; Post, SR; Chun, J. (1996) 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. [PMID:8922387]

9. Heise, CE; Santos, WL; Schreihofer, AM; Heasley, BH; Mukhin, YV; Macdonald, TL; Lynch, KR. (2001) Activity of 2-substituted lysophosphatidic acid (LPA) analogs at LPA receptors: discovery of a LPA1/LPA3 receptor antagonist. Mol. Pharmacol., 60 (6): 1173-80. [PMID:11723223]

10. 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]

11. Qian, L; Xu, Y; Simper, T; Jiang, G; Aoki, J; Umezu-Goto, M; Arai, H; Yu, S; Mills, GB; Tsukahara, R; et al.. (2006) Phosphorothioate analogues of alkyl lysophosphatidic acid as LPA3 receptor-selective agonists. ChemMedChem, 1 (3): 376-83. [PMID:16892372]

12. 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]

13. Yang, AH; Ishii, I; Chun, J. (2002) In vivo roles of lysophospholipid receptors revealed by gene targeting studies in mice. Biochim. Biophys. Acta, 1582 (1-3): 197-203. [PMID:12069829]

To cite this database page, please use the following:

Chido Mpamhanga.
Lysophospholipid (LPA) receptors: LPA1 receptor. Last modified on 31/01/2013. Accessed on 23/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=272.


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