GPER

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G protein-coupled estrogen receptor 1
Identifiers
Symbols GPER1 ; CEPR; CMKRL2; DRY12; FEG-1; GPCR-Br; GPER; GPR30; LERGU; LERGU2; LyGPR; mER
External IDs OMIM601805 MGI1924104 HomoloGene15855 IUPHAR: ChEMBL: 5872 GeneCards: GPER1 Gene
RNA expression pattern
PBB GE GPR30 210640 s at tn.png
PBB GE GPR30 211829 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2852 76854
Ensembl ENSG00000164850 ENSMUSG00000053647
UniProt Q99527 Q8BMP4
RefSeq (mRNA) NM_001031682 NM_029771
RefSeq (protein) NP_001035055 NP_084047
Location (UCSC) Chr 7:
1.12 – 1.13 Mb
Chr 5:
139.42 – 139.43 Mb
PubMed search [1] [2]

G protein-coupled estrogen receptor 1 (GPER), formerly referred to as G protein-coupled receptor 30 (GPR30), is a G protein-coupled receptor that in humans is encoded by the GPER gene.[1] GPER is an integral membrane protein with high affinity for estradiol, though not for other endogenous estrogens, such as estrone or estriol, nor for other endogenous steroids, including progesterone, testosterone, and cortisol.[2][3][4][5] However, GPER does show high affinity for aldosterone.[6]

Function[edit]

This protein is a member of the rhodopsin-like family of G protein-coupled receptors and is a multi-pass membrane protein that localizes to the endoplasmic reticulum. The protein binds estradiol, resulting in intracellular calcium mobilization and synthesis of phosphatidylinositol (3,4,5)-trisphosphate in the nucleus. This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estradiol. Alternate transcriptional splice variants that encode the same protein have been characterized.[7] The distribution of GPER is well established in the rodent, with high expression observed in the hypothalamus, pituitary gland, adrenal medulla, kidney medulla and developing follicles of the ovary.[8]

Animal studies[edit]

Female GPER knockout mice display hyperglycemia and impaired glucose tolerance, reduced body growth, and increased blood pressure.[9] Male GPER knockout mice are observed to have increased growth, body fat, increased osteoblast function (mineralization) resulting in higher bone mineral density and trabecular bone volume, and persistent growth plate activity resulting in longer bones.[10]

Clinical significance[edit]

GPER plays an important role in development of tamoxifen resistance in breast cancer cells.[11]

References[edit]

  1. ^ O'Dowd BF, Nguyen T, Marchese A, Cheng R, Lynch KR, Heng HH, Kolakowski LF, George SR (January 1998). "Discovery of three novel G-protein-coupled receptor genes". Genomics 47 (2): 310–3. doi:10.1006/geno.1998.5095. PMID 9479505. 
  2. ^ Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER (2005). "A transmembrane intracellular estrogen receptor mediates rapid cell signaling". Science 307 (5715): 1625–30. doi:10.1126/science.1106943. PMID 15705806. 
  3. ^ Filardo EJ, Thomas P (2005). "GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release". Trends Endocrinol. Metab. 16 (8): 362–7. doi:10.1016/j.tem.2005.08.005. PMID 16125968. 
  4. ^ Manavathi B, Kumar R (2006). "Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin". J. Cell. Physiol. 207 (3): 594–604. doi:10.1002/jcp.20551. PMID 16270355. 
  5. ^ Prossnitz ER, Arterburn JB, Sklar LA (2007). "GPR30: A G protein-coupled receptor for estrogen". Mol. Cell. Endocrinol. 265-266: 138–42. doi:10.1016/j.mce.2006.12.010. PMC 1847610. PMID 17222505. 
  6. ^ Wendler A, Albrecht C, Wehling M (August 2012). "Nongenomic actions of aldosterone and progesterone revisited". Steroids 77 (10): 1002–6. doi:10.1016/j.steroids.2011.12.023. PMID 22285849. 
  7. ^ "Entrez Gene: GPR30 G protein-coupled receptor 30". 
  8. ^ Hazell GG, Yao ST, Roper JA, Prossnitz ER, O'Carroll AM, Lolait SJ (August 2009). "Localisation of GPR30, a novel G protein-coupled oestrogen receptor, suggests multiple functions in rodent brain and peripheral tissues". J. Endocrinol. 202 (2): 223–36. doi:10.1677/JOE-09-0066. PMC 2710976. PMID 19420011. 
  9. ^ Mårtensson UE, Salehi SA, Windahl S, Gomez MF, Swärd K, Daszkiewicz-Nilsson J, Wendt A, Andersson N, Hellstrand P, Grände PO, Owman C, Rosen CJ, Adamo ML, Lundquist I, Rorsman P, Nilsson BO, Ohlsson C, Olde B, Leeb-Lundberg LM (2008). "Deletion of the G protein-coupled Receptor GPR30 Impairs Glucose Tolerance, Reduces Bone Growth, Increases Blood Pressure, and Eliminates Estradiol-stimulated Insulin Release in Female Mice". Endocrinology 150 (2): 687–98. doi:10.1210/en.2008-0623. PMID 18845638. 
  10. ^ Ford J, Hajibeigi A, Long M, Hahner L, Gore C, Hsieh JT, Clegg D, Zerwekh J, Oz OK (August 2010). "GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice". J Bone Miner Res 26 (2): 298–307. doi:10.1002/jbmr.209. PMID 20734455. 
  11. ^ Ignatov A, Ignatov T, Roessner A, Costa SD, Kalinski T (2010). "Role of GPR30 in the mechanisms of tamoxifen resistance in breast cancer MCF-7 cells". Breast Cancer Research and Treatment 123 (1): 87–96. doi:10.1007/s10549-009-0624-6. PMID 19911269. 

Further reading[edit]

  • Filardo EJ (2002). "Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer". J. Steroid Biochem. Mol. Biol. 80 (2): 231–8. doi:10.1016/S0960-0760(01)00190-X. PMID 11897506. 
  • Filardo EJ, Thomas P (2005). "GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release". Trends Endocrinol. Metab. 16 (8): 362–7. doi:10.1016/j.tem.2005.08.005. PMID 16125968. 
  • Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
  • Owman C, Blay P, Nilsson C, Lolait SJ (1996). "Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt's lymphoma and widely distributed in brain and peripheral tissues". Biochem. Biophys. Res. Commun. 228 (2): 285–92. doi:10.1006/bbrc.1996.1654. PMID 8920907. 
  • Feng Y, Gregor P (1997). "Cloning of a novel member of the G protein-coupled receptor family related to peptide receptors". Biochem. Biophys. Res. Commun. 231 (3): 651–4. doi:10.1006/bbrc.1997.6161. PMID 9070864. 
  • Kvingedal AM, Smeland EB (1997). "A novel putative G-protein-coupled receptor expressed in lung, heart and lymphoid tissue". FEBS Lett. 407 (1): 59–62. doi:10.1016/S0014-5793(97)00278-0. PMID 9141481. 
  • Carmeci C, Thompson DA, Ring HZ, et al. (1998). "Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer". Genomics 45 (3): 607–17. doi:10.1006/geno.1997.4972. PMID 9367686. 
  • Takada Y, Kato C, Kondo S, et al. (1998). "Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress". Biochem. Biophys. Res. Commun. 240 (3): 737–41. doi:10.1006/bbrc.1997.7734. PMID 9398636. 
  • Filardo EJ, Quinn JA, Bland KI, Frackelton AR (2001). "Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF". Mol. Endocrinol. 14 (10): 1649–60. doi:10.1210/me.14.10.1649. PMID 11043579. 
  • Filardo EJ, Quinn JA, Frackelton AR, Bland KI (2002). "Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis". Mol. Endocrinol. 16 (1): 70–84. doi:10.1210/me.16.1.70. PMID 11773440. 
  • Ahola TM, Purmonen S, Pennanen P, et al. (2002). "Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells". Eur. J. Biochem. 269 (10): 2485–90. doi:10.1046/j.1432-1033.2002.02912.x. PMID 12027886. 
  • Ahola TM, Manninen T, Alkio N, Ylikomi T (2002). "G protein-coupled receptor 30 is critical for a progestin-induced growth inhibition in MCF-7 breast cancer cells". Endocrinology 143 (9): 3376–84. doi:10.1210/en.2001-211445. PMID 12193550. 
  • Ahola TM, Alkio N, Manninen T, Ylikomi T (2002). "Progestin and G protein-coupled receptor 30 inhibit mitogen-activated protein kinase activity in MCF-7 breast cancer cells". Endocrinology 143 (12): 4620–6. doi:10.1210/en.2002-220492. PMID 12446589. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Scherer SW, Cheung J, MacDonald JR, et al. (2003). "Human chromosome 7: DNA sequence and biology". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205. 
  • Hamza A, Sarma MH, Sarma RH (2004). "Plausible interaction of an alpha-fetoprotein cyclopeptide with the G-protein-coupled receptor model GPR30: docking study by molecular dynamics simulated annealing". J. Biomol. Struct. Dyn. 20 (6): 751–8. doi:10.1080/07391102.2003.10506892. PMID 12744705. 
  • Kanda N, Watanabe S (2003). "17Beta-estradiol enhances the production of nerve growth factor in THP-1-derived macrophages or peripheral blood monocyte-derived macrophages". J. Invest. Dermatol. 121 (4): 771–80. doi:10.1046/j.1523-1747.2003.12487.x. PMID 14632195. 
  • Kanda N, Watanabe S (2004). "17beta-estradiol inhibits oxidative stress-induced apoptosis in keratinocytes by promoting Bcl-2 expression". J. Invest. Dermatol. 121 (6): 1500–9. doi:10.1111/j.1523-1747.2003.12617.x. PMID 14675202. 

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.