Receptor glukagonu sličnog peptida 1

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Receptor glukagonu sličnog peptida 1‎‎

Prikaz bazira na PDB 3C59.
Dostupne strukture
3C59, 3C5T, 3IOL
Identifikatori
SimboliGLP1R; MGC138331
Vanjski IDOMIM: 138032 MGI: 99571 HomoloGene: 1558 IUPHAR: GLP-1 GeneCards: GLP1R Gene
Ontologija gena
Molekularna funkcija • aktivnost transmembranskog signalnog receptora
• aktivnost glukagonskog receptora
• aktivnosti G-protein spregnutog peptidnog receptora
• vezivanje peptidnog hormona
Celularna komponenta • ćelijska membrana
• integralno sa ćelijskom membranom
• integralno sa membranom
Biološki proces • metabolički proces energetske rezerve
• signalni put G-protein spregnutog receptor aktiviranog adenilat ciklazom
• aktivacija adenilat ciklazne aktivnosti
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez274014652
EnsemblENSG00000112164ENSMUSG00000024027
UniProtP43220E9Q7I1
RefSeq (mRNA)NM_002062.3NM_021332.2
RefSeq (protein)NP_002053.3NP_067307.2
Lokacija (UCSC)Chr 6:
39.02 - 39.06 Mb		Chr 17:
31.04 - 31.07 Mb
PubMed pretraga[1][2]

Receptor glukagonu sličnog peptida 1 (GLP1R) je ljudski gen koji se nalazi na hromozomu 6.[1][2] Ovaj protein je član glukogenske receptorske familije G protein spregnutih receptora.[3]

Specifičnost liganda

GLP1R specifično vezuje glukagonu sličan peptid-1 (GLP1) i ima mnogo manji afinitet za srodne peptide kao što su gastrični inhibitorni polipeptid i glukagon.[4]

Funkcija i terapeutski potencijal

GLP1R je izražen u pancreasnim beta ćelijama. Aktivirani GLP1R stimuliše adenilil ciklazni put što dovodi do povišene sinteze i otpuštanja insulina.[5] Consequently GLP1R has been suggested as a potential target for the treatment of dijabetes.[6]

GLP1R je isto tako izražen u mozgu gde učestvuje u kontroli apetita.[7] Miševi kod kojih je GLP1R izrađen u povećanoj meri pokazuju poboljšanu memoriju i sposobnost učenja.[8]

Reference

  1. ↑ Thorens B (September 1992). „Expression cloning of the pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1”. Proc. Natl. Acad. Sci. U.S.A. 89 (18): 8641–5. DOI:10.1073/pnas.89.18.8641. PMC 49976. PMID 1326760. 
  2. ↑ Dillon JS, Tanizawa Y, Wheeler MB, Leng XH, Ligon BB, Rabin DU, Yoo-Warren H, Permutt MA, Boyd AE 3rd (October 1993). „Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor”. Endocrinology 133 (4): 1907–10. DOI:10.1210/en.133.4.1907. PMID 8404634. 
  3. ↑ Brubaker PL, Drucker DJ (2002). „Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors” (PDF). Recept. Channels 8 (3-4): 179–88. DOI:10.1080/10606820213687. PMID 12529935. Pristupljeno 2008-07-14. 
  4. ↑ Fehmann HC, Jiang J, Schweinfurth J, Dörsch K, Wheeler MB, Boyd AE 3rd, Göke B (April 1994). „Ligand-specificity of the rat GLP-I receptor recombinantly expressed in Chinese hamster ovary (CHO-) cells”. Z Gastroenterol 32 (4): 203–7. PMID 8017094. 
  5. ↑ Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF (May 1987). „Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line”. Proc. Natl. Acad. Sci. U.S.A. 84 (10): 3434–8. DOI:10.1073/pnas.84.10.3434. PMC 304885. PMID 3033647. 
  6. ↑ Holst JJ (May 2004). „Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors”. Expert Opin Emerg Drugs 9 (1): 155–66. DOI:10.1517/eoed.9.1.155.32952. PMID 15155141. 
  7. ↑ Kinzig KP, D'Alessio DA, Seeley RJ (2002-12-01). „The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness”. J. Neurosci. 22 (23): 10470–6. PMID 12451146. 
  8. ↑ During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN (September 2003). „Glucagon-like peptide-1 receptor is involved in learning and neuroprotection”. Nat. Med. 9 (9): 1173–9. DOI:10.1038/nm919. PMID 12925848. 

Literatura

  • van Eyll B, Lankat-Buttgereit B, Bode HP, et al. (1994). „Signal transduction of the GLP-1-receptor cloned from a human insulinoma”. FEBS Lett. 348 (1): 7–13. DOI:10.1016/0014-5793(94)00553-2. PMID 7517895. 
  • Gromada J, Rorsman P, Dissing S, Wulff BS (1995). „Stimulation of cloned human glucagon-like peptide 1 receptor expressed in HEK 293 cells induces cAMP-dependent activation of calcium-induced calcium release”. FEBS Lett. 373 (2): 182–6. DOI:10.1016/0014-5793(95)01070-U. PMID 7589461. 
  • Wei Y, Mojsov S (1995). „Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences”. FEBS Lett. 358 (3): 219–24. DOI:10.1016/0014-5793(94)01430-9. PMID 7843404. 
  • Lankat-Buttgereit B, Göke R, Stöckmann F, et al. (1994). „Detection of the human glucagon-like peptide 1(7-36) amide receptor on insulinoma-derived cell membranes”. Digestion 55 (1): 29–33. DOI:10.1159/000201119. PMID 8112494. 
  • Graziano MP, Hey PJ, Borkowski D, et al. (1993). „Cloning and functional expression of a human glucagon-like peptide-1 receptor”. Biochem. Biophys. Res. Commun. 196 (1): 141–6. DOI:10.1006/bbrc.1993.2226. PMID 8216285. 
  • Stoffel M, Espinosa R, Le Beau MM, Bell GI (1993). „Human glucagon-like peptide-1 receptor gene. Localization to chromosome band 6p21 by fluorescence in situ hybridization and linkage of a highly polymorphic simple tandem repeat DNA polymorphism to other markers on chromosome 6”. Diabetes 42 (8): 1215–8. DOI:10.2337/diabetes.42.8.1215. PMID 8392011. 
  • Dillon JS, Tanizawa Y, Wheeler MB, et al. (1993). „Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor”. Endocrinology 133 (4): 1907–10. DOI:10.1210/en.133.4.1907. PMID 8404634. 
  • Thorens B, Porret A, Bühler L, et al. (1993). „Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor”. Diabetes 42 (11): 1678–82. DOI:10.2337/diabetes.42.11.1678. PMID 8405712. 
  • Lankat-Buttgereit B, Göke B (1997). „Cloning and characterization of the 5' flanking sequences (promoter region) of the human GLP-1 receptor gene”. Peptides 18 (5): 617–24. DOI:10.1016/S0196-9781(97)00001-6. PMID 9213353. 
  • Frimurer TM, Bywater RP (1999). „Structure of the integral membrane domain of the GLP1 receptor”. Proteins 35 (4): 375–86. DOI:10.1002/(SICI)1097-0134(19990601)35:4<375::AID-PROT1>3.0.CO;2-2. PMID 10382665. 
  • Huypens P, Ling Z, Pipeleers D, Schuit F (2001). „Glucagon receptors on human islet cells contribute to glucose competence of insulin release”. Diabetologia 43 (8): 1012–9. DOI:10.1007/s001250051484. PMID 10990079. 
  • Hartley JL, Temple GF, Brasch MA (2001). „DNA cloning using in vitro site-specific recombination”. Genome Res. 10 (11): 1788–95. DOI:10.1101/gr.143000. PMC 310948. PMID 11076863. 
  • Xiao Q, Jeng W, Wheeler MB (2001). „Characterization of glucagon-like peptide-1 receptor-binding determinants”. J. Mol. Endocrinol. 25 (3): 321–35. DOI:10.1677/jme.0.0250321. PMID 11116211. 
  • Bazarsuren A, Grauschopf U, Wozny M, et al. (2003). „In vitro folding, functional characterization, and disulfide pattern of the extracellular domain of human GLP-1 receptor”. Biophys. Chem. 96 (2-3): 305–18. DOI:10.1016/S0301-4622(02)00023-6. PMID 12034449. 
  • 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. 
  • Mungall AJ, Palmer SA, Sims SK, et al. (2003). „The DNA sequence and analysis of human chromosome 6”. Nature 425 (6960): 805–11. DOI:10.1038/nature02055. PMID 14574404. 
  • Tokuyama Y, Matsui K, Egashira T, et al. (2005). „Five missense mutations in glucagon-like peptide 1 receptor gene in Japanese population”. Diabetes Res. Clin. Pract. 66 (1): 63–9. DOI:10.1016/j.diabres.2004.02.004. PMID 15364163. 
  • 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. 
  • Jorgensen R, Martini L, Schwartz TW, Elling CE (2005). „Characterization of glucagon-like peptide-1 receptor beta-arrestin 2 interaction: a high-affinity receptor phenotype”. Mol. Endocrinol. 19 (3): 812–23. DOI:10.1210/me.2004-0312. PMID 15528268. 
  • Mahon MJ, Shimada M (2005). „Calmodulin interacts with the cytoplasmic tails of the parathyroid hormone 1 receptor and a sub-set of class b G-protein coupled receptors”. FEBS Lett. 579 (3): 803–7. DOI:10.1016/j.febslet.2004.12.056. PMID 15670850. 

Vidi još

Spoljašnje veze

  • „Glucagon Receptor Family: GLP-1”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-03-03. 
  • MeSH glucagon-like+peptide+receptor
  • p
  • r
  • u
Klasa A: Rodopsinu slični
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat  • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6)  • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Drugi
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)