Opioid growth factor receptor, also known as OGFr or the ζ-opioid receptor, is a protein which in humans is encoded by the OGFRgene.[5][6] The protein encoded by this gene is a receptor for opioid growth factor (OGF), also known as [Met(5)]-enkephalin. The endogenous ligand is thus a known opioid peptide, and OGFr was originally discovered and named as a new opioid receptor zeta (ζ). However it was subsequently found that it shares little sequence similarity with the other opioid receptors, and has quite different function.
The natural function of this receptor appears to be in regulation of tissue growth,[7][8][9][10] and it has been shown to be important in embryonic development,[11] wound repair,[12] and certain forms of cancer.[13][14][15][16]
OGF is a negative regulator of cell proliferation and tissue organization in a variety of processes. The encoded unbound receptor for OGF has been localized to the outer nuclear envelope, where it binds OGF and is translocated into the nucleus. The coding sequence of this gene contains a polymorphic region of 60 nt tandem imperfect repeat units. Several transcripts containing between zero and eight repeat units have been reported.[5]
Mechanism of activationedit
The opioid growth factor receptor consists of a chain of 677 amino acids, which includes a nuclear localization sequence region. When OGF binds to the receptor, an OGF-OGFr complex is formed, which leads to the increase in the synthesis of the selective cyclin-dependent kinase (CDK) inhibitor proteins, p12 and p16. Retinoblastoma protein becomes inactivated through phosphorylation by CDKs, and leads to the progression of the cell cycle from the G1 phase to the S phase. Because the activation of the OGF receptor, blocks the phosphorylation of retinoblastoma proteins, retardation of the G1 phase occurs, which prevents the cell from further dividing.[17][18]
Therapeutic applicationsedit
Upregulation of OGFr and consequent stimulation of the OGF-OGFr system are important for the anti-proliferative effects of imidazoquinoline drugs like imiquimod and resiquimod, which are immune response modifiers with potent antiviral and antitumour effects, used as topical creams for the treatment of skin cancers and warts.[19]
^Zagon IS, Verderame MF, Allen SS, McLaughlin PJ (February 2000). "Cloning, sequencing, chromosomal location, and function of cDNAs encoding an opioid growth factor receptor (OGFr) in humans". Brain Res. 856 (1–2): 75–83. doi:10.1016/S0006-8993(99)02330-6. PMID 10677613. S2CID 37516655.
^Wu Y, McLaughlin PJ, Zagon IS (April 1998). "Ontogeny of the opioid growth factor, Met5-enkephalin, preproenkephalin gene expression, and the zeta opioid receptor in the developing and adult aorta of rat". Dev. Dyn. 211 (4): 327–37. doi:10.1002/(SICI)1097-0177(199804)211:4<327::AID-AJA4>3.0.CO;2-J. PMID 9566952.
^ abZagon IS, Verderame MF, McLaughlin PJ (February 2002). "The biology of the opioid growth factor receptor (OGFr)". Brain Res. Brain Res. Rev. 38 (3): 351–76. doi:10.1016/S0165-0173(01)00160-6. PMID 11890982. S2CID 37812525.
^Malendowicz LK, Rebuffat P, Tortorella C, Nussdorfer GG, Ziolkowska A, Hochol A (May 2005). "Effects of met-enkephalin on cell proliferation in different models of adrenocortical-cell growth". Int. J. Mol. Med. 15 (5): 841–5. doi:10.3892/ijmm.15.5.841. PMID 15806307.
^Cheng F, McLaughlin PJ, Verderame MF, Zagon IS (January 2009). "The OGF-OGFr axis utilizes the p16INK4a and p21WAF1/CIP1 pathways to restrict normal cell proliferation". Molecular Biology of the Cell. 20 (1): 319–27. doi:10.1091/mbc.E08-07-0681. PMC2613082. PMID 18923142.
^Zagon IS, Wu Y, McLaughlin PJ (August 1999). "Opioid growth factor and organ development in rat and human embryos". Brain Res. 839 (2): 313–22. doi:10.1016/S0006-8993(99)01753-9. PMID 10519055. S2CID 22000619.
^Sassani JW, Zagon IS, McLaughlin PJ (May 2003). "Opioid growth factor modulation of corneal epithelium: uppers and downers". Curr. Eye Res. 26 (5): 249–62. doi:10.1076/ceyr.26.4.249.15427. PMID 12854052. S2CID 34449136.
^Zagon IS, Smith JP, McLaughlin PJ (March 1999). "Human pancreatic cancer cell proliferation in tissue culture is tonically inhibited by opioid growth factor". Int. J. Oncol. 14 (3): 577–84. doi:10.3892/ijo.14.3.577. PMID 10024694.
^McLaughlin PJ, Levin RJ, Zagon IS (May 1999). "Regulation of human head and neck squamous cell carcinoma growth in tissue culture by opioid growth factor". Int. J. Oncol. 14 (5): 991–8. doi:10.3892/ijo.14.5.991. PMID 10200353.
^Cheng F, Zagon IS, Verderame MF, McLaughlin PJ (November 2007). "The opioid growth factor (OGF)-OGF receptor axis uses the p16 pathway to inhibit head and neck cancer". Cancer Research. 67 (21): 10511–8. doi:10.1158/0008-5472.CAN-07-1922. PMID 17974995.
^Donahue RN, McLaughlin PJ, Zagon IS (March 2009). "Cell Proliferation of Human Ovarian Cancer is Regulated by the Opioid Growth Factor - Opioid Growth Factor Receptor Axis". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 296 (6): R1716–25. doi:10.1152/ajpregu.00075.2009. PMID 19297547.
^Zagon IS, Donahue RN, McLaughlin PJ (2009). "Opioid growth factor-opioid growth factor receptor axis is a physiological determinant of cell proliferation in diverse human cancers". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 297 (4): R1154–61. doi:10.1152/ajpregu.00414.2009. PMID 19675283.
^Avella DM, Kimchi ET, Donahue RN, Tagaram HR, McLaughlin PJ, Zagon IS, Staveley-O'Carroll KF (2010). "The opioid growth factor-opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 298 (2): R459–66. doi:10.1152/ajpregu.00646.2009. PMC2828179. PMID 19923357.
^Zagon IS, Donahue RN, Rogosnitzky M, McLaughlin PJ (August 2008). "Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function". Experimental Biology and Medicine. 233 (8): 968–79. doi:10.3181/0802-RM-58. PMID 18480416. S2CID 35164284.
Further readingedit
Zagon IS, Verderame MF, McLaughlin PJ (2002). "The biology of the opioid growth factor receptor (OGFr)". Brain Res. Brain Res. Rev. 38 (3): 351–76. doi:10.1016/S0165-0173(01)00160-6. PMID 11890982. S2CID 37812525.
Zagon IS, Verderame MF, Allen SS, McLaughlin PJ (2000). "Cloning, sequencing, chromosomal location, and function of cDNAs encoding an opioid growth factor receptor (OGFr) in humans". Brain Res. 856 (1–2): 75–83. doi:10.1016/S0006-8993(99)02330-6. PMID 10677613. S2CID 37516655.
Wu CJ, Yang XF, McLaughlin S, et al. (2000). "Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia". J. Clin. Invest. 106 (5): 705–14. doi:10.1172/JCI10196. PMC381287. PMID 10974024.
Hattori A, Okumura K, Nagase T, et al. (2001). "Characterization of long cDNA clones from human adult spleen". DNA Res. 7 (6): 357–66. doi:10.1093/dnares/7.6.357. PMID 11214971.
Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. Bibcode:2001Natur.414..865D. doi:10.1038/414865a. PMID 11780052.
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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
Zagon IS, Ruth TB, Leure-duPree AE, et al. (2003). "Immunoelectron microscopic localization of the opioid growth factor receptor (OGFr) and OGF in the cornea". Brain Res. 967 (1–2): 37–47. doi:10.1016/S0006-8993(02)04172-0. PMID 12650964. S2CID 30270018.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC528928. PMID 15489334.
McLaughlin PJ, Zagon IS (2006). "Progression of squamous cell carcinoma of the head and neck is associated with down-regulation of the opioid growth factor receptor". Int. J. Oncol. 28 (6): 1577–83. doi:10.3892/ijo.28.6.1577. PMID 16685459.
Zagon IS, McLaughlin PJ (2006). "Opioid growth factor receptor is unaltered with the progression of human pancreatic and colon cancers". Int. J. Oncol. 29 (2): 489–94. doi:10.3892/ijo.29.2.489. PMID 16820893.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
McLaughlin PJ, Verderame MF, Hankins JL, Zagon IS (2007). "Overexpression of the opioid growth factor receptor downregulates cell proliferation of human squamous carcinoma cells of the head and neck". Int. J. Mol. Med. 19 (3): 421–8. doi:10.3892/ijmm.19.3.421. PMID 17273790.
This article incorporates text from the public domain Pfam and InterPro: IPR006757
This article incorporates text from the public domain Pfam and InterPro: IPR006770
January 01, 1970
ogfr, opioid, growth, factor, receptor, also, known, opioid, receptor, protein, which, humans, encoded, ogfr, gene, protein, encoded, this, gene, receptor, opioid, growth, factor, also, known, enkephalin, endogenous, ligand, thus, known, opioid, peptide, origi. Opioid growth factor receptor also known as OGFr or the z opioid receptor is a protein which in humans is encoded by the OGFR gene 5 6 The protein encoded by this gene is a receptor for opioid growth factor OGF also known as Met 5 enkephalin The endogenous ligand is thus a known opioid peptide and OGFr was originally discovered and named as a new opioid receptor zeta z However it was subsequently found that it shares little sequence similarity with the other opioid receptors and has quite different function OGFRIdentifiersAliasesOGFR OGFr opioid growth factor receptorExternal IDsOMIM 606459 MGI 1919325 HomoloGene 7199 GeneCards OGFRGene location Human Chr Chromosome 20 human 1 Band20q13 33Start62 804 835 bp 1 End62 814 000 bp 1 Gene location Mouse Chr Chromosome 2 mouse 2 Band2 2 H4Start180 231 038 bp 2 End180 237 629 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmonocytesural nerveright lobe of liverspleenright lungright uterine tubecingulate gyrusgastric mucosaupper lobe of left lungBrodmann area 9Top expressed inyolk sacmaxillary prominencethymusinternal carotid arteryganglionic eminenceexternal carotid arteryprimitive streakspermatocytesomiteabdominal wallMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein binding G protein coupled opioid receptor activity signaling receptor activityCellular componentmembrane cytoplasm nucleus cellular componentBiological processregulation of growth regulation of cell growth G protein coupled opioid receptor signaling pathway signal transductionSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez1105472075EnsemblENSG00000060491ENSMUSG00000049401UniProtQ9NZT2Q99PG2RefSeq mRNA NM 007346NM 031373RefSeq protein NP 031372NP 113550Location UCSC Chr 20 62 8 62 81 MbChr 2 180 23 180 24 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Opioid growth factor receptor OGFr conserved regionIdentifiersSymbolOGFr NPfamPF04664InterProIPR006757Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary Opioid growth factor receptor repeatIdentifiersSymbolOGFr IIIPfamPF04680InterProIPR006770Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary Contents 1 Function 2 Mechanism of activation 3 Therapeutic applications 4 Structure 5 References 6 Further readingFunction editThe natural function of this receptor appears to be in regulation of tissue growth 7 8 9 10 and it has been shown to be important in embryonic development 11 wound repair 12 and certain forms of cancer 13 14 15 16 OGF is a negative regulator of cell proliferation and tissue organization in a variety of processes The encoded unbound receptor for OGF has been localized to the outer nuclear envelope where it binds OGF and is translocated into the nucleus The coding sequence of this gene contains a polymorphic region of 60 nt tandem imperfect repeat units Several transcripts containing between zero and eight repeat units have been reported 5 Mechanism of activation editThe opioid growth factor receptor consists of a chain of 677 amino acids which includes a nuclear localization sequence region When OGF binds to the receptor an OGF OGFr complex is formed which leads to the increase in the synthesis of the selective cyclin dependent kinase CDK inhibitor proteins p12 and p16 Retinoblastoma protein becomes inactivated through phosphorylation by CDKs and leads to the progression of the cell cycle from the G1 phase to the S phase Because the activation of the OGF receptor blocks the phosphorylation of retinoblastoma proteins retardation of the G1 phase occurs which prevents the cell from further dividing 17 18 Therapeutic applications editUpregulation of OGFr and consequent stimulation of the OGF OGFr system are important for the anti proliferative effects of imidazoquinoline drugs like imiquimod and resiquimod which are immune response modifiers with potent antiviral and antitumour effects used as topical creams for the treatment of skin cancers and warts 19 Structure editOGF contains a conserved N terminal domain followed by a series of imperfect repeats 8 References edit a b c GRCh38 Ensembl release 89 ENSG00000060491 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000049401 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Entrez Gene OGFR opioid growth factor receptor Zagon IS Verderame MF Allen SS McLaughlin PJ February 2000 Cloning sequencing chromosomal location and function of cDNAs encoding an opioid growth factor receptor OGFr in humans Brain Res 856 1 2 75 83 doi 10 1016 S0006 8993 99 02330 6 PMID 10677613 S2CID 37516655 Wu Y McLaughlin PJ Zagon IS April 1998 Ontogeny of the opioid growth factor Met5 enkephalin preproenkephalin gene expression and the zeta opioid receptor in the developing and adult aorta of rat Dev Dyn 211 4 327 37 doi 10 1002 SICI 1097 0177 199804 211 4 lt 327 AID AJA4 gt 3 0 CO 2 J PMID 9566952 a b Zagon IS Verderame MF McLaughlin PJ February 2002 The biology of the opioid growth factor receptor OGFr Brain Res Brain Res Rev 38 3 351 76 doi 10 1016 S0165 0173 01 00160 6 PMID 11890982 S2CID 37812525 Malendowicz LK Rebuffat P Tortorella C Nussdorfer GG Ziolkowska A Hochol A May 2005 Effects of met enkephalin on cell proliferation in different models of adrenocortical cell growth Int J Mol Med 15 5 841 5 doi 10 3892 ijmm 15 5 841 PMID 15806307 Cheng F McLaughlin PJ Verderame MF Zagon IS January 2009 The OGF OGFr axis utilizes the p16INK4a and p21WAF1 CIP1 pathways to restrict normal cell proliferation Molecular Biology of the Cell 20 1 319 27 doi 10 1091 mbc E08 07 0681 PMC 2613082 PMID 18923142 Zagon IS Wu Y McLaughlin PJ August 1999 Opioid growth factor and organ development in rat and human embryos Brain Res 839 2 313 22 doi 10 1016 S0006 8993 99 01753 9 PMID 10519055 S2CID 22000619 Sassani JW Zagon IS McLaughlin PJ May 2003 Opioid growth factor modulation of corneal epithelium uppers and downers Curr Eye Res 26 5 249 62 doi 10 1076 ceyr 26 4 249 15427 PMID 12854052 S2CID 34449136 Zagon IS Smith JP McLaughlin PJ March 1999 Human pancreatic cancer cell proliferation in tissue culture is tonically inhibited by opioid growth factor Int J Oncol 14 3 577 84 doi 10 3892 ijo 14 3 577 PMID 10024694 McLaughlin PJ Levin RJ Zagon IS May 1999 Regulation of human head and neck squamous cell carcinoma growth in tissue culture by opioid growth factor Int J Oncol 14 5 991 8 doi 10 3892 ijo 14 5 991 PMID 10200353 Cheng F Zagon IS Verderame MF McLaughlin PJ November 2007 The opioid growth factor OGF OGF receptor axis uses the p16 pathway to inhibit head and neck cancer Cancer Research 67 21 10511 8 doi 10 1158 0008 5472 CAN 07 1922 PMID 17974995 Donahue RN McLaughlin PJ Zagon IS March 2009 Cell Proliferation of Human Ovarian Cancer is Regulated by the Opioid Growth Factor Opioid Growth Factor Receptor Axis American Journal of Physiology Regulatory Integrative and Comparative Physiology 296 6 R1716 25 doi 10 1152 ajpregu 00075 2009 PMID 19297547 Zagon IS Donahue RN McLaughlin PJ 2009 Opioid growth factor opioid growth factor receptor axis is a physiological determinant of cell proliferation in diverse human cancers American Journal of Physiology Regulatory Integrative and Comparative Physiology 297 4 R1154 61 doi 10 1152 ajpregu 00414 2009 PMID 19675283 Avella DM Kimchi ET Donahue RN Tagaram HR McLaughlin PJ Zagon IS Staveley O Carroll KF 2010 The opioid growth factor opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer American Journal of Physiology Regulatory Integrative and Comparative Physiology 298 2 R459 66 doi 10 1152 ajpregu 00646 2009 PMC 2828179 PMID 19923357 Zagon IS Donahue RN Rogosnitzky M McLaughlin PJ August 2008 Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function Experimental Biology and Medicine 233 8 968 79 doi 10 3181 0802 RM 58 PMID 18480416 S2CID 35164284 Further reading editZagon IS Verderame MF McLaughlin PJ 2002 The biology of the opioid growth factor receptor OGFr Brain Res Brain Res Rev 38 3 351 76 doi 10 1016 S0165 0173 01 00160 6 PMID 11890982 S2CID 37812525 Zagon IS Verderame MF Allen SS McLaughlin PJ 2000 Cloning sequencing chromosomal location and function of cDNAs encoding an opioid growth factor receptor OGFr in humans Brain Res 856 1 2 75 83 doi 10 1016 S0006 8993 99 02330 6 PMID 10677613 S2CID 37516655 Wu CJ Yang XF McLaughlin S et al 2000 Detection of a potent humoral response associated with immune induced remission of chronic myelogenous leukemia J Clin Invest 106 5 705 14 doi 10 1172 JCI10196 PMC 381287 PMID 10974024 Hattori A Okumura K Nagase T et al 2001 Characterization of long cDNA clones from human adult spleen DNA Res 7 6 357 66 doi 10 1093 dnares 7 6 357 PMID 11214971 Deloukas P Matthews LH Ashurst J et al 2002 The DNA sequence and comparative analysis of human chromosome 20 Nature 414 6866 865 71 Bibcode 2001Natur 414 865D doi 10 1038 414865a PMID 11780052 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 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Zagon IS Ruth TB Leure duPree AE et al 2003 Immunoelectron microscopic localization of the opioid growth factor receptor OGFr and OGF in the cornea Brain Res 967 1 2 37 47 doi 10 1016 S0006 8993 02 04172 0 PMID 12650964 S2CID 30270018 Ota T Suzuki Y Nishikawa T et al 2004 Complete sequencing and characterization of 21 243 full length human cDNAs Nat Genet 36 1 40 5 doi 10 1038 ng1285 PMID 14702039 Gerhard DS Wagner L Feingold EA et al 2004 The status quality and expansion of the NIH full length cDNA project the Mammalian Gene Collection MGC Genome Res 14 10B 2121 7 doi 10 1101 gr 2596504 PMC 528928 PMID 15489334 McLaughlin PJ Zagon IS 2006 Progression of squamous cell carcinoma of the head and neck is associated with down regulation of the opioid growth factor receptor Int J Oncol 28 6 1577 83 doi 10 3892 ijo 28 6 1577 PMID 16685459 Zagon IS McLaughlin PJ 2006 Opioid growth factor receptor is unaltered with the progression of human pancreatic and colon cancers Int J Oncol 29 2 489 94 doi 10 3892 ijo 29 2 489 PMID 16820893 Olsen JV Blagoev B Gnad F et al 2006 Global in vivo and site specific phosphorylation dynamics in signaling networks Cell 127 3 635 48 doi 10 1016 j cell 2006 09 026 PMID 17081983 S2CID 7827573 McLaughlin PJ Verderame MF Hankins JL Zagon IS 2007 Overexpression of the opioid growth factor receptor downregulates cell proliferation of human squamous carcinoma cells of the head and neck Int J Mol Med 19 3 421 8 doi 10 3892 ijmm 19 3 421 PMID 17273790 This article incorporates text from the public domain Pfam and InterPro IPR006757 This article incorporates text from the public domain Pfam and InterPro IPR006770 Retrieved from https en wikipedia org w index php title OGFr amp oldid 1119104425, wikipedia, wiki, book, books, library,
