PT  - JOURNAL ARTICLE
AU  - Dong-Soon Im
AU  - Christopher E. Heise
AU  - Michael A. Harding
AU  - Susan R. George
AU  - Brian F. O'Dowd
AU  - Dan Theodorescu
AU  - Kevin R. Lynch
TI  - Molecular Cloning and Characterization of a Lysophosphatidic Acid Receptor, Edg-7, Expressed in Prostate
AID  - 10.1124/mol.57.4.753
DP  - 2000 Apr 01
TA  - Molecular Pharmacology
PG  - 753--759
VI  - 57
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/57/4/753.short
4100  - http://molpharm.aspetjournals.org/content/57/4/753.full
SO  - Mol Pharmacol2000 Apr 01; 57
AB  - Two G protein-coupled receptors (Edg-2) and (Edg-4) for the lysolipid phosphoric acid mediator lysophosphatidic acid have been described by molecular cloning. However, the calcium-mobilizing receptor Edg-4 is not expressed in some cell lines that exhibit robust calcium responses to this ligand, thus predicting the existence of additional receptor subtypes. We report here on the characterization of a third human lysophosphatidic acid receptor subtype, Edg-7, which mediates lysophosphatidic acid-evoked calcium mobilization. In a rat hepatoma Rh7777 cell line that lacks endogenous responses to lysophosphatidic acid, this lipid mediator, but not others, evokes calcium transients when the cells have been transfected with Edg-7 or Edg-4 DNAs. Furthermore, frog oocytes exhibit a calcium-mediated chloride conductance in response to mammalian-selective lysophosphatidic acid mimetics after injection of Edg-7 mRNA. Edg-7-expressing Rh7777 cells do not show inhibition of forskolin-driven rises in cAMP in response to lysophosphatidic acid. However, membranes from HEK293T cells cotransfected with Edg-7 and Gi2α protein DNAs show lysophosphatidic acid dose-dependent increases in [γ-35S]GTP binding with an EC50 value of 195 nM. When we used this assay to compare various synthetic LPA analogs at Edg-2, Edg-4, and Edg-7 receptors, we found that ethanolamine-based compounds, which are full LPA mimetics at Edg-2 and Edg-4, exhibit little activity at the Edg-7 receptor. Edg-7 RNA was detected in extracts of several rat and human tissues including prostate. Together, our data indicate that Edg-7 is a third lysophosphatidic acid receptor that couples predominantly to Gq/11α proteins.