Genomic Characterization of the Lysophosphatidic Acid Receptor Gene, lpA2/Edg4, and Identification of a Frameshift Mutation in a Previously Characterized cDNA

Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: Over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer

“…Fitting results were also identified for more distant markers, D19S221 localized to 19p13 42 and D19S224 localized to 19q13. 43,44 These results confirm those of Contos et al 41 Experiments in 8 primary thyroid cultures derived from goiters consistently showed that LPA stimulates thyroid cell proliferation in vitro under serum-free conditions. The concentrations needed to achieve this effect ranged between 1 and 100 M and are in concordance with findings in many other cell types, where the proliferative effects of LPA are maximal at these concentrations, whereas effects on other physiological variables occur at a considerably lower concentration of even less than 1 M. [45][46][47] The effects of LPA were not observed in the presence of 5% FBS.…”

“…16 Random sequencing of human cosmid libraries yielded a DNA sequence of a putative novel G protein-coupled receptor on chromosome 19 (gi:2213634), identified as the genomic EDG4 receptor sequence. 41 We demonstrated by direct sequencing of PCR products that the human genomic DNA sequence is identical with the cosmid sequence. The mRNA sequence expressed in the human thyroid and in human fetal liver was identical with the genomic EDG4 sequence yielding the 351-amino acid version of the protein.…”

“…Different cDNA sequences of the EDG4 receptor have previously been reported: GenBank accession AAF43409 for the regular 351-amino acid version (Bandoh K. et al, unpublished data) corresponding to the previously identified genomic sequence 41 and GenBank accession NM_004720 encoding a 382-amino acid version. 16 We verified the genomic and mRNA sequence obtained from thyroid tissue by sequencing of the EDG4M amplimer, which spans 35111-35378 of the genomic sequence of the cosmid R33799 (GenBank 2213634) containing the EDG4 receptor genomic sequence, and found identity with the cosmid sequence.…”

Lysophosphatidic Acid Induces αvβ6 Integrin-Mediated TGF-β Activation via the LPA2 Receptor and the Small G Protein Gαq

“…There is 50% embryological lethality in lpa1 Ϫ/Ϫ mice whereas LPA2 expression is low in normal tissue, and lpa2 Ϫ/Ϫ mice displayed no obvious phenotypic abnormalities. 56,57 Recently it has been shown that lpa1 Ϫ/Ϫ mice are protected from bleomycin-induced fibrosis. The proposed mechanism for this is via reduced vascular leak and fibroblast chemotaxis with LPA1 coupling to the small G protein G␣ i .…”

Tandem genomic arrangement of a G protein (Gna15) and G protein‐coupled receptor (s1p4/lpC1/Edg6) gene

“…PCR, restriction digestion, and backcross panel analysis were done as described previously [9], except primers used to amplify genomic DNA were edg7h (5P-CGTGTTTAAGAATGAAAGGG-3P) and edg7n (5P-GGAG-TTGTAGGCACACTTA-3P). Raw data can be viewed at http:// www.jax.org/resources/documents/cmdata.…”