Identification of an EDG7 Variant, HOFNH30, a G-Protein-Coupled Receptor for Lysophosphatidic Acid

Fitzgerald, Laura Rydelek; Dytko, George; Sarau, Henry M.; Mannan, Ishrat Jahan; Ellis, Catherine; Lane, Pamela; Tan, K. B.; Murdock, Paul R.; Wilson, Shelagh; Bergsma, Derk J.; Ames, Robert S.; Foley, James J.; Campbell, David A.; McMillan, Lynnette; Evans, Nina; Elshourbagy, Nabil A.; Minehart, Heather; Tsui, Ping

doi:10.1006/bbrc.2000.2943

Cited by 18 publications

(10 citation statements)

References 21 publications

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“…Lysophosphatidic acid-binding EDG receptors have also been reported for cardiomyocytes (EDG-2 and -4), developing neurons and oligodendrocytes and brain white matter (EDG-2), ovarian cancer cell lines and T-cells, and brain neuronal cells (EDG-4) (6,26). EDG-7 is highly expressed in prostate (29).…”

Section: Discussionmentioning

confidence: 98%

Endothelial Differentiation Gene Receptors in Pancreatic Islets and INS-1 Cells

2003

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The endothelial differentiation gene (EDG) receptors are a class of G protein-coupled receptors. EDG-1, -3, -5, -6, and -8 bind the bioactive lipid sphingosine-1-phosphate (SPP) as the primary signaling ligand. EDG-2, -4, and -7 bind the ligand lysophosphatidic acid. EDG-1, -2, -3, -5, -6, and -7, but not -8, mRNAs were expressed in isolated rat pancreatic islets, whereas INS-1 insulinoma cells expressed only EDG-1, -2, -3, and -5 mRNAs. EDG-4 mRNA was expressed in mouse islets. EDG-1 mRNA but not EDG-3 mRNA was rapidly induced relative to 18S rRNA after stimulation of isolated islets with phorbol 12-myristate 13-acetate (PMA) or cholecystokinin-8S for 2 h. The protein kinase C inhibitor GF 109203X blocked the EDG-1 induction by PMA. Similarly, in islets stimulated for 2 h with 17 mmol/l glucose, the relative EDG-1 mRNA levels increased almost twofold compared with levels in control islets at 5.5 mmol/l glucose. In contrast, after 11 mmol/l glucose stimulation for 7 days, the relative levels of rat islet EDG-1 mRNA were significantly reduced to 54% below that of islets cultured at 5.5 mmol/l glucose. There was no change in relative EDG-3 mRNA levels. Stimulation of EDG receptors in islets and INS-1 cells with SPP inhibited glucagon-like peptide 1 (GLP-1)-stimulated cAMP production and insulin secretion in a concentration-dependent manner. Pertussis toxin antagonized the SPP effects on insulin release. Thus, EDG receptors are expressed in pancreatic islet ␤-cells and G i seems to mediate the inhibition by SPP of adenylyl cyclase and cAMP formation and inhibition of the stimulation of insulin secretion by GLP-1. Diabetes

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Section: Discussionmentioning

confidence: 98%

Endothelial Differentiation Gene Receptors in Pancreatic Islets and INS-1 Cells

2003

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“…In recombinant LPA receptor-expressing cells, LPS was not shown to be an agonist for LPA 1 , LPA 2 and LPA 3 receptors (An et al, 1998a(An et al, , 1998bBandoh et al, 1999;Fitzgerald et al, 2000). Furthermore, an agonistic property of LPS to LPA receptors has been excluded in an L2071 mouse fibroblast cell line .…”

Section: Discussionmentioning

confidence: 93%

“…In recombinant derived LPA receptor-expressing cells, LPS was not shown to be agonistic for the LPA 1 , LPA 2 and LPA 3 receptors (An et al, 1998a(An et al, , 1998bBandoh et al, 1999;Fitzgerald et al, 2000). In addition, An et al (1998a) demonstrated that LPS failed to stimulate serum responsive element-driven luciferase expression in LPA 1 and LPA 2 -transfected Jurkat cells and Bandoh et al (1999) reported that LPS failed to stimulate [Ca 2+ ] i increase in LPA 3 -transfected Sf9 cells.…”

Section: Introductionmentioning

confidence: 99%

Lysophosphatidylserine induces calcium signaling through Ki16425/VPC32183-sensitive GPCR in bone marrow-derived mast cells and in C6 glioma and colon cancer cells

Kim

Lee

et al. 2008

Arch. Pharm. Res.

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Lysophosphatidylserine (LPS) can be generated following phosphatidylserine-specific phospholipase A2 activation. The effects of LPS on cellular activities and the identities of its target molecules, however, have not been fully elucidated. In this study, we observed that LPS stimulated intracellular calcium increased in mouse bone marrow-derived mast cells (BMMC), and rat C6 glioma and human HCT116 colon cancer cells and compared the LPS-induced Ca2+ increases with the response by lysophosphatidic acid (LPA), a structurally related bioactive lysolipid. In order to test involvement of signaling molecules in the LPS-induced Ca2+ signaling, we used pertussis toxin (PTX), U73122, and 2-APB, which are specific inhibitors for G proteins, phospholipase C (PLC), and IP3 receptors, respectively. The increases due to LPS and LPA were inhibited by PTX, U-73122 and 2-APB, suggesting that both lipids stimulate calcium signaling via G proteins (Gi/o types), PLC activation, and subsequent IP3 production, although the sensitivity to pharmacological inhibitors varied from complete inhibition to partial inhibition depending on cell type and lysolipid. Furthermore, we observed that Ki16425 completely inhibited an LPS-induced Ca2+ response in three cell types, but that the effect of VPC32183 varied from complete inhibition in BMMC and C6 glioma cells to partial inhibition in HCT116 cells. Therefore, we conclude that LPS increases [Ca2+]i through Ki16425/VPC32183-sensitive G protein-coupled receptors (GPCR), G protein, PLC, and IP3 in mouse BMMC, rat C6, and human HCT116 cells.

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“…These same modifications resulted in inactive compounds when the LPA3 splice variant, HOFNH30, was expressed in RBL-2H3 cells [3]. In whole animal assays in rats, replacement of X with choline, ethanol, propanol, or methanol results in hypotension, rather than the hypertension normally induced by LPA [13].…”

Section: Lpa Receptor Agonist Sarmentioning

confidence: 99%

“…During the last decade, enormous progress has been made in identifying and characterizing the cellular receptors specific for the phospholipid growfli factor lysophosphatidic acid (LPA) [1][2][3][4][5][6]. Three of these receptors, LPAi/EDG2, LPA2/EDG4, and LPA3/EDG7, are members of the endothelial differentiation gene (EDO) family and share 30-35% homology with sphingosine-1-phosphate (SIP) receptors in the same family (S1P,/EDG1, SIP2/EDG5, SIP3/EDG3, SIP4/EDG6, SIP5/EDG8).…”

Section: Introductionmentioning

confidence: 99%

Computational Modeling of the Prostate-Expressed Lysophosphatidic Acid Receptor Edg-7

Sardar¹,

Parrill²

2003

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Public reporting burden for this collection of infonnation is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sourx;es, gathering and maintaining the data needed, and completing and reviewing this collection of infonnation. Send comments regarding this burden estimate or any other aspect of this collection of Infonnation, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Infonmatlon Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arilr^gton, VA 22202-4302, and to the Office of Management and Budnet,, Washington, DC 20503 AGENCY USE ONLY (Leave blank)2. REPORT DATE April 2003 REPORT TYPE AND DATES COVEREDAnnual Summary (15 Mar 02 -14 Mar 03) TITLE AND SUBTITLEComputational Modeling of the Prostate-Expressed Lysophosphatidic Acid Receptor Edg-76. AUTHOR(S):Vineet M. Sardar, Ph.D. Abby L. Parrill, Ph.D. FUNDING NUMBERSDAMD17-02-1-0248 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)The University of Memphis Memphis, Tennessee 38152 E-Mall:vsardar@Memphis.edu Recently it was shown that the lysophosphatidic acid (LPA) receptor LPAs/EDG? is expressed in human prostate cancer cell lines namely LNCap and Du-145. Based on these findings and evidence that LPA is a very potent mitogen, the overall goal of this proposed research is to rationally design LPAs/EDG? selective ligands. We have identified the probable binding position of two LPAi/EDG2 and LPAa/EDG? selective inhibitors namely DGPP (8:0) and FAP (12:0). The binding position and the critical amino acids involved in interacting with these inhibitors relative to the endogenous ligand LPA (18:1) is discussed. PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)U SUBJECT TERMS:Edg-7, computational modeling, acid receptor We explored the binding site and assessed the critical amino acid interactions of antagonists and agonists by docking to the inactive and active form of the receptor respectively.The antagonists, DGPP (8:0) and FAP (12:0), were docked against the inactive receptor models.The agonists, R-LPA (18:1) and S-LPA (18:1) were docked against the active receptor models.One hundred complexes of receptor-ligand pair were generated, in order to evaluate the binding The R and S isomers of LPA (18:1) were docked against the active model of LPA3 to assess the stereo-selectivity of the receptor. A previous study showed that the R and S isomers of 1-C16-GP (Figure 1) were equaUy active in mobilizing Ca^^ in RH7777 cells stably expressing LPAi, LPA2, and LPAa.^^ Based on our results as shovra in Table 1 we do not see any differences in energy with respect to R and S isomer. On assessing the complex of the R isomer of LPA (18:1) with the active form of LPA3 receptor we observe that the polar phosphate ftinctionality is in close proximity to ion-pair with R105 and R276. We also observe that the hydroxyl group at the sn-2 position is in a position to form hydrogen bond with Q106 as shown in figure 4. ...

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Identification of an EDG7 Variant, HOFNH30, a G-Protein-Coupled Receptor for Lysophosphatidic Acid

Cited by 18 publications

References 21 publications

Endothelial Differentiation Gene Receptors in Pancreatic Islets and INS-1 Cells

Endothelial Differentiation Gene Receptors in Pancreatic Islets and INS-1 Cells

Lysophosphatidylserine induces calcium signaling through Ki16425/VPC32183-sensitive GPCR in bone marrow-derived mast cells and in C6 glioma and colon cancer cells

Computational Modeling of the Prostate-Expressed Lysophosphatidic Acid Receptor Edg-7

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