Alternative titles; symbols
HGNC Approved Gene Symbol: LPAR2
Cytogenetic location: 19p13.11 Genomic coordinates (GRCh38): 19:19,623,655-19,628,220 (from NCBI)
The lysophospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P; see 601974), are important extracellular signaling molecules. These lipid mediators are pleiotropic; among the most common cellular responses are mitogenesis, cell survival (antiapoptosis), inhibition of adenylyl cyclase, and calcium mobilization. Physiologic events associated with these mediators include platelet aggregation, vasopressor activity, wound healing, immune modulation, and angiogenesis. Many of the actions of LPA and S1P are mediated through a set of G protein-coupled receptors, including EDG4 (summary by Chun et al., 2002).
Chun et al. (2002) proposed a nomenclature scheme for the LPA and S1P receptors that is consistent with the International Union of Pharmacology (IUP) guidelines. According to these guidelines, a receptor is to be named with the abbreviation of the natural agonist with the highest potency, followed by a subscripted arabic number. Thus they suggested that the designation EDG4 should be changed to LPA2.
By searching an EST database for sequences similar to EDG2 (602282), An et al. (1998) identified a cDNA encoding EDG4. Sequence analysis predicted that the 382-amino acid EDG4 protein, which shares 46% amino acid identity with EDG2, contains 7 hydrophobic segments, potential N-glycosylation sites in the N terminus, and potential serine/threonine kinase phosphorylation sites in the intracellular portion. Expression of EDG4 mediated increased transcription of the serum response element (SRE) reporter gene in response to LPA and PA. Northern blot analysis detected an 8-kb EDG4 transcript in peripheral blood leukocytes, thymus, spleen, and all tumor types, as well as a 1.8-kb transcript in leukocytes, testis, prostate, pancreas, and adherent cancer cell lines. Little or no expression was detected in brain, heart, placenta, and digestive tract, tissues where EDG2 expression is abundant.
Using the aequorin luminescence method to reduce nonspecific signals, An et al. (1998) determined that LPA induced increased calcium mobilization in cells expressing EDG2 or EDG4, probably through inositol triphosphate generated by phospholipase C activation. EDG4-mediated calcium mobilization utilizes both Gi (see GNAI1; 139310) and Gq (see GNAQ; 600998) proteins, whereas EDG2 utilizes pertussis toxin-sensitive Gi proteins only.
By RT-PCR and Western blot analysis, Goetzl et al. (2000) showed that CD4+ T cells and B cells but not CD8+ T cells express EDG4. Stimulation of CD4+ but not CD8+ T cells in the presence of LPA or monoclonal anti-N-terminal EDG4 suppressed interleukin-2 (IL2; 147680) secretion.
Contos and Chun (2000) cloned the mouse cDNA encoding Edg4. Genomic sequence analysis determined that the human and mouse EDG4 genes contain 3 exons.
An et al. (1998) stated that the EDG4 gene maps to chromosome 19p12. Contos and Chun (2000) mapped the mouse Edg4 gene to central chromosome 8.
An, S., Bleu, T., Hallmark, O. G., Goetzl, E. J. Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. J. Biol. Chem. 273: 7906-7910, 1998. [PubMed: 9525886] [Full Text: https://doi.org/10.1074/jbc.273.14.7906]
An, S., Bleu, T., Zheng, Y., Goetzl, E. J. Recombinant human G protein-coupled lysophosphatidic acid receptors mediate intracellular calcium mobilization. Molec. Pharm. 54: 881-888, 1998. [PubMed: 9804623] [Full Text: https://doi.org/10.1124/mol.54.5.881]
Chun, J., Goetzl, E. J., Hla, T., Igarashi, Y., Lynch, K. R., Moolenaar, W., Pyne, S., Tigyi, G. International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature. Pharm. Rev. 54: 265-269, 2002. [PubMed: 12037142] [Full Text: https://doi.org/10.1124/pr.54.2.265]
Contos, J. J. A., Chun, J. Genomic characterization of the lysophosphatidic acid receptor gene, Ip(A2)/Edg4, and identification of a frameshift mutation in a previously characterized cDNA. Genomics 64: 155-169, 2000. [PubMed: 10729222] [Full Text: https://doi.org/10.1006/geno.2000.6122]
Goetzl, E. J., Kong, Y., Voice, J. K. Cutting edge: differential constitutive expression of functional receptors for lysophosphatidic acid by human blood lymphocytes. J. Immun. 164: 4996-4999, 2000. [PubMed: 10799850] [Full Text: https://doi.org/10.4049/jimmunol.164.10.4996]