Disease relevance of EDG7

• Neither the EDG7- nor EDG4-transduced Ca(2+) response or cAMP accumulation was inhibited by pertussis toxin [1].
• Edg4 and Edg7 levels are consistently increased in malignant ovarian epithelial cells contributing to the aberrant response of ovarian cancer cells to LPA [2].
• Northern blot analysis revealed that various gastric cancer cells expressed variable levels of LPA1, LPA2, and LPA3 without a consistent pattern [3].
• The results of these studies suggest that RRV ORF74 encodes a GPCR with properties similar to those of its homologue in HHV-8 and that this gene may play a role in RRV-associated pathogenesis [4].
• 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 [5].

Psychiatry related information on EDG7

• Given the complexity of neurological disorders such as ischemic stroke, Alzheimer's disease and epilepsy, exploitation mGlu receptor-associated GPCR interactions may prove efficacious in the treatment of such disorders [6].

High impact information on EDG7

• Future high-resolution structural studies of rhodopsin and other GPCRs will form a basis to elucidate the detailed molecular mechanism of GPCR-mediated signal transduction [7].
• Significantly, GPCR-containing CCPs are also functionally distinct, as their surface residence time is regulated locally by GPCR cargo via PDZ-dependent linkage to the actin cytoskeleton [8].
• Our results reveal a novel function of betaarr1 as a cytoplasm-nucleus messenger in GPCR signaling and elucidate an epigenetic mechanism for direct GPCR signaling from cell membrane to the nucleus through signal-dependent histone modification [9].
• (2005) provide evidence that beta-arrestin 1 moves to the nucleus in response to GPCR stimulation, where it regulates gene expression by facilitating histone acetylation at specific gene promoters [10].
• A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription [9].

Chemical compound and disease context of EDG7

• We demonstrate that in squamous cell carcinoma cells, stimulation with the GPCR agonists LPA or carbachol specifically results in metalloprotease cleavage and release of amphiregulin (AR) [11].
• In addition to their physiological roles in the cardiovascular system (CVS), G-protein-coupled receptor (GPCR) agonists such as noradrenaline, endothelin-1 and angiotensin II (Ang II) are known to be involved in the development of cardiac hypertrophy [12].
• This induction of permissive SOCE in response to soluble E-selectin and PAF was shown to act through a G protein-coupled receptor (GPCR) coupled to pertussis toxin-insensitive G(q/11) [13].
• In PC12 rat pheochromocytoma cells, both agents block lysophosphatidic acid (LPA)- and bradykinin-stimulated Erk 1/2 phosphorylation, suggesting that intact focal adhesion complexes are required for GPCR-induced mitogen-activated protein kinase activation in these cells [14].
• Here we report that a synthetic peptide derived from the NH2-terminal extracellular region of an orphan GPCR, GPR1 (GPR1ntP-(1-27); MEDLEETLFEEFENYSYDLDYYSLESC), inhibited infection of not only an HIV-1 variant that uses GPR1 as a co-receptor, but also X4, R5, and R5X4 viruses [15].

Biological context of EDG7

• We examined the structure-activity relationship of cloned lysophosphatidic acid (LPA) receptors (endothelial cell differentiation gene (EDG) 2, EDG4, and EDG7) by measuring [Ca(2+)](i) in Sf9 insect cells expressing each receptor using LPA with various acyl chains bound at either the sn-1 or the sn-2 position of the glycerol backbone [16].
• Comparative studies in sparse and dense cell density indicated that EDG-7 was positively associated, whereas EDG-2 was negatively associated with cell proliferation rate [17].
• EDG-7 maximally expressed at sparse cell density and minimally expressed in dense cell population [17].
• Using a Boyden chamber assay, LPA markedly increased cell migration of LPA1-expressing cells, the effects of which were almost totally abrogated by Ki16425, an LPA antagonist against LPA1 and LPA3 [3].
• Here we show that sphingosine-1-phosphate (S1P)-induced endothelial cell migration requires the Akt-mediated phosphorylation of the G protein-coupled receptor (GPCR) EDG-1 [18].

Anatomical context of EDG7

• In PC12 cells, EDG4 but not EDG2 or EDG7 mediated the activation of MAP kinase by LPA [1].
• We suggest that EDG-7 regulates LPA-mediated mesangial cell proliferation [17].
• By contrast, LPA detected in seminal plasma, which contains a low concentration of albumin, selectively activated EDG7 [19].
• EDG4 was overexpressed in all cancer cell lines studied relative to that in IOSE-29 cells, but EDG7 was overexpressed in only two lines [20].
• We showed by reverse transcription and PCR that human eosinophils express the mRNA of the LPA receptors endothelial differentiation gene (EDG)-2 and EDG-7 [21].

Associations of EDG7 with chemical compounds

• Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid [1].
• LPAs with an unsaturated fatty acid but not with a saturated fatty acid induced an increase in the [Ca(2+)](i) of EDG7-expressing Sf9 cells, whereas LPAs with both saturated and unsaturated fatty acids elicited a Ca(2+) response in Sf9 cells expressing EDG4 [1].
• For EDG7 the highest reactivity was observed with LPA with Delta9-unsaturated fatty acid (oleic (18:1), linoleic (18:2), and linolenic (18:3)) at sn-2 followed by 2-palmitoleoyl (16:1) and 2-arachidonoyl (20:4) LPA [16].
• Dioctanoylglycerol pyrophosphate, an antagonist for EDG-7, almost completely inhibited mesangial cell proliferation induced by LPA [17].
• One compound with a bulky hydrophobic group (VPC12249) was a dual LPA1/LPA3 competitive antagonist [22].

Physical interactions of EDG7

• There is increasing evidence that LPA signaling reprograms gene expression, but the GPCR-induced pathways connecting LPA receptor stimulation to downstream transcription factors are not well characterized [23].

Regulatory relationships of EDG7

• KSHV-GPCR induced the tyrosine phosphorylation of RAFTK [24].
• The activation of EDG7 was further enhanced when the cells were treated with phorbol ester or a bacterial phospholipase D, suggesting involvement of phospholipase D in the process [25].

Other interactions of EDG7

• In EDG7- or EDG4-expressing Sf9 cells, LPA stimulated forskolin-induced increase in intracellular cAMP levels, which was not observed in EDG2-expressing cells [1].
• METHODS: Expression of cyclin D1 and LPA receptors (EDG4 and EDG7) was determined in six ovarian cancer cell lines (including OVCAR-3 cells) and immortalized ovarian surface epithelial cells (IOSE-29) [20].
• RAFTK also mediated the KSHV-GPCR-induced activation of Lyn, a Src family kinase [24].
• This review summarizes structural features and signal transduction properties of GLP-1 and its cognate beta-cell GPCR [26].
• GPCR regulation of PTEN maybe a general mechanism in signaling events of cell migration and invasion [27].

Analytical, diagnostic and therapeutic context of EDG7

• RT-PCR analysis demonstrated that HOFNH30 mRNA is expressed in placenta whereas EDG7 mRNA shows highest expression in prostate [28].
• Graded reductions in GPCR expression can be achieved through antisense strategies or total gene ablation or replacement can be achieved through gene targeting strategies, and exogenous expression of wild-type or mutant GPCR isoforms can be accomplished with transgenic technologies [29].
• Techniques: GPCR assembly, pharmacology and screening by flow cytometry [30].
• In the present study we demonstrate the formation of an agonist-induced multimeric complex containing a GPCR, betaarrestin 2, and the beta2-adaptin subunit of AP-2. beta2-Adaptin binds betaarrestin 2 in a yeast two-hybrid assay and coimmunoprecipitates with betaarrestins and beta2AR in an agonist-dependent manner in HEK-293 cells [31].
• In addition, Rho is the only GPCR for which the presumed higher-order oligomeric state has been demonstrated, by imaging native disk membranes using atomic force microscopy (AFM) [32].

References