Discovery of Three Novel G-Protein-Coupled Receptor Genes

O’Dowd, Brian F.; Nguyen, Tuan; Marchese, Adriano; Cheng, Regina; Lynch, Kevin R.; Heng, Henry H.Q.; Kolakowski, Lee F.; George, Susan R.

doi:10.1006/geno.1998.5095

Cited by 270 publications

(206 citation statements)

References 18 publications

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“…Importantly, GPR30 is abundantly expressed in ERα-positive breast cancer cells, with little or no expression detected in ERα-negative cells (Carmeci et al, 1997). Northern blot and in situ hybridization analysis has revealed that GPR30 is expressed in most tissues and distributed throughout many different brain regions (O'Dowd et al, 1998). In the rat, we have also independently confirmed at GPR30 mRNA and protein is widely distributed and is detected in most tissues.…”

Section: Gpr30 As a Rapidly Acting Mersupporting

confidence: 57%

Rapid signaling mechanisms of estrogens in the developing cerebellum

Belcher

2008

Brain Research Reviews

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The steroid hormone 17β-Estradiol regulates the normal function and development of the mammalian nervous system. Many of estradiol's effects are mediated via the nuclear hormone estrogen receptors ERα and ERβ. In addition to regulating estrogen-responsive gene expression, estradiol also acts in an immediate and cell-specific fashion to regulate various intracellular signal transduction pathways. The goal of this review is to develop a contextual framework to understand the generalized function of estrogen during development of brain regions not known to be sexually specialized. However, it is first important to build this generalized framework on the more well-developed foundation of estrogen's gonad-driven sex-specific actions. As a result, a discussion of known and proposed mechanisms of estrogen actions in reproductive and other tissues will be presented. Building upon this information, a review of our research group's recent in vitro and in vivo studies that have focused on elucidating the mechanisms of estrogen actions in neurons of the non-sexually specialized cerebellum will be presented. While the full-spectrum of estrogen action during normal cerebellar development remains unresolved, results of recent studies have revealed a pathologic role for estrogen and estrogen receptors in medulloblastoma, common pediatric brain tumors that arise from cerebellar granule cell-like precursors. The potential use of anti-estrogen signaling agents as adjuvant therapy for medulloblastoma is proposed based on those finding.

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Section: Gpr30 As a Rapidly Acting Mersupporting

confidence: 57%

Rapid signaling mechanisms of estrogens in the developing cerebellum

Belcher

2008

Brain Research Reviews

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“…In the late 1990's, a putative GPCR was cloned by 4 different groups using highly disparate approaches (Carmeci et al, 1997;O'Dowd et al, 1998;Owman et al, 1996;Takada et al, 1997). The GPCR identified in these studies displayed little homology to other GPCRs.…”

Section: G Protein-coupled Seven Transmembrane Estrogen Receptorsmentioning

confidence: 99%

GPR30: A G protein-coupled receptor for estrogen

Prossnitz

Arterburn

Sklar

2007

Molecular and Cellular Endocrinology

268

186

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Estrogen is a critical steroid in human physiology exerting its effect both at the transcriptional level as well as at the level of rapid intracellular signaling through second messengers. Many of estrogen's transcriptional effects have long been known to be mediated through classical nuclear steroid receptors but recent studies also demonstrate the existence of a 7-transmembrane G protein-coupled receptor, GPR30 that responds to estrogen with rapid cellular signaling. There is currently controversy over the ability of classical estrogen receptors to recapitulate GPR30-mediated signaling mechanisms and vice versa. This article will summarize recent literature and address the relationship between GPR30 and conventional estrogen receptor signaling.

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“…NM_001505) which was mapped on 7p22.3. (23) When the mutation search was carried out to check if the subtracted clone, the GPR30 3′UTR fragment (approximately 300 bp) would contain genomic aberration, we identified a 2 bpdeletion (Cytosine and Thymine; CT) in the genomic DNA pair of gastric cancer. The database search showed that the 2 bpdeleted GPR30 had been reported as 'FEG-1' (Accession No.…”

Section: Resultsmentioning

confidence: 99%

Cloning of novel LERGU mRNAs in GPR30 3′ untranslated region and detection of 2 bp‐deletion polymorphism in gastric cancer

et al. 2005

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The improved IGCR (In-Gel Competitive Reassociation) method was applied to the analysis of human gastric cancer genomic DNA to identify its alterations, and it appeared that the IGCR library contained a fragment of 3′ ′ ′ ′-untranslated region (3′ ′ ′ ′ UTR) of G-protein coupled receptor 30 (GPR30) mRNA. When we searched genomic DNA pairs of gastric cancer patients with this IGCR clone, we found the deletion polymorphism with or without 2 bp (Cytosine and Thymine; CT). We confirmed the existence of a novel mRNA in GPR30 3′ ′ ′ ′UTR by northern blotting, cloned this novel mRNA and named it Leucine Rich Protein in GPR30 3′ ′ ′ ′UTR (LERGU). The EST database search gave one alternative splicing form in this 3′ ′ ′ ′ UTR, which was named as LERGU-1. A novel alternative splicing form of this mRNA was also identified from the stomach total RNA, which was named LERGU-2. The LERGU mRNA was also detected in eight gastric cancer cell lines, but GPR30 mRNA scarcely existed. Furthermore, we detected the 2 bp-deletion form in genomic DNAs and mRNAs derived from gastric cancers, but not in other type cancers. Since the 2 bp-deletion position on LERGU corresponds to its alternative splicing site, this deletion may produce a frame-shifted protein. G astric cancer is the most frequent malignancy of the gastrointestinal tract in Japanese and certain South-east Asian populations, and one of the leading causes of cancer mortality in the world. Genetic aberrations associated with gastric cancers have been reported in the gene encoding Ecadherin, p53, the transforming growth factor-β receptor and so on, but it is believed that a much greater number of genetic changes could account for the phenomena.(1-4)The original In-Gel Competitive Reassociation (IGCR) technique is one of the DNA subtractive hybridization techniques, which consists of the size separation of double strand DNA fragments by electrophoresis, the denaturation in gel with an alkaline buffer and the renaturation by exchanging the buffer. (5)(6)(7)(8)(9)(10)(11) This technique had achieved the sufficient enrichment of the DNA sequences only in the target to detect small aberrations between two DNA populations such as recombination junctions in extrachromosomal DNA, (9) restriction fragment length polymorphism in the genome, (10) and methylation sites in the genome.(6) We have improved the IGCR technique to overcome several disadvantages such as time-consuming and complex process with poor reproducibility. In the denaturing step, we employed a heat denature method instead of the alkaline denature protocol. In addition, to reduce the genomic complexity and prevent the amplification of undesirable polymerase chain reaction (PCR) bands, smaller fragments were cut off with DNA binding resins in the purification of Mse I cut fragment mixture, and a 'competitor' was introduced to the IGCR technique. Our improved IGCR method efficiently detected Epstein-Barr virus (EBV) genomic DNA fragments, which were contained only in a tester DNA of gastric cancer. (12) G protein coupled rece...

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Discovery of Three Novel G-Protein-Coupled Receptor Genes

Cited by 270 publications

References 18 publications

Rapid signaling mechanisms of estrogens in the developing cerebellum

Rapid signaling mechanisms of estrogens in the developing cerebellum

GPR30: A G protein-coupled receptor for estrogen

Cloning of novel LERGU mRNAs in GPR30 3′ untranslated region and detection of 2 bp‐deletion polymorphism in gastric cancer

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