Glukagonski receptor
Glukagonski receptor je 62 kDa težak protein koji se aktivira glukagonom. On je član klase B G protein spregnutih receptora. On formira spregu sa G alfa i, Gs i u manjoj meri G alfa q.[1] Stimulacija receptora dovodi do aktivacije adenilat ciklaze i povišenja nivoa intracelularnog cAMP. Kod ljudi, glukagonski receptor je kodiran GCGR genom.[2][3]
| Glukagonski receptor | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Dostupne strukture | |||||||||||
| 3CZF | |||||||||||
| Identifikatori | |||||||||||
| Simboli | GCGR; GGR | ||||||||||
| Vanjski ID | OMIM: 138033 MGI: 99572 HomoloGene: 131 IUPHAR: glucagon GeneCards: GCGR Gene | ||||||||||
| |||||||||||
| Ortolozi | |||||||||||
| Vrsta | Čovek | Miš | |||||||||
| Entrez | 2642 | 14527 | |||||||||
| Ensembl | ENSG00000215644 | ENSMUSG00000025127 | |||||||||
| UniProt | P47871 | Q61606 | |||||||||
| RefSeq (mRNA) | NM_000160.3 | NM_008101.2 | |||||||||
| RefSeq (protein) | NP_000151.1 | NP_032127.2 | |||||||||
| Lokacija (UCSC) |
Chr 17: 79.76 - 79.77 Mb |
Chr 11: 120.39 - 120.4 Mb | |||||||||
| PubMed pretraga | [1] | [2] | |||||||||
Glukagonski receptori su uglavnom izraženi u jetri i bugrezima, i u manjim razmeri u srcu, adipoznom tkivu, slezini, grudnoj žledi, nadbubrežnim žlezdama, pankreasu, cerebralnom korteksu, i gastrointestinalnom traktu.
Klinički zanačaj уреди
Jedna od mutacija GCGR gena je vezana za dijabetes melitus tip 2.[4]
Inaktivirajuća mutacija glukagonskog receptora kod ljudi uzrokuje otpornost na glukagon, te je povezana sa hiperplazijom pankreasnih alfa ćelija, nezidioblastozom, hiperglukagonemijom, i pankreasnim neuroendokrinim tumorima.[5]
Reference уреди
- ^ 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”. Recept. Channels. 8 (3-4): 179—88. PMID 12529935. doi:10.1080/10606820213687.
- ^ Lok S, Kuijper JL, Jelinek LJ, Kramer JM, Whitmore TE, Sprecher CA, Mathewes S, Grant FJ, Biggs SH, Rosenberg GB (1994). „The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization”. Gene. 140 (2): 203—9. PMID 8144028. doi:10.1016/0378-1119(94)90545-2.
- ^ Menzel S, Stoffel M, Espinosa R, Fernald AA, Le Beau MM, Bell GI (1994). „Localization of the glucagon receptor gene to human chromosome band 17q25”. Genomics. 20 (2): 327—8. PMID 8020989. doi:10.1006/geno.1994.1179.
- ^ Hager J, Hansen L, Vaisse C, Vionnet N, Philippi A, Poller W, Velho G, Carcassi C, Contu L, Julier C (1995). „A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus”. Nat. Genet. 9 (3): 299—304. PMID 7773293. doi:10.1038/ng0395-299.
- ^ Zhou C, Dhall D, Nissen NN, Chen CR, Yu R (2009). „Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor.”. Pancreas. 38 (8): 941—6. PMC 2767399
. PMID 19657311. doi:10.1097/MPA.0b013e3181b2bb03.
Literatura уреди
- Levey GS, Weiss SR, Ruiz E (1975). „Characterization of the glucagon receptor in a pheochromocytoma.”. J. Clin. Endocrinol. Metab. 40 (4): 720—3. PMID 165216. doi:10.1210/jcem-40-4-720.
- Nakamura S, Rodbell M (1991). „Glucagon induces disaggregation of polymer-like structures of the alpha subunit of the stimulatory G protein in liver membranes.”. Proc. Natl. Acad. Sci. U.S.A. 88 (16): 7150—4. PMC 52251 . PMID 1908089. doi:10.1073/pnas.88.16.7150.
- Horuk R, Wright DE (1983). „Partial purification and characterization of the glucagon receptor.”. FEBS Lett. 155 (2): 213—7. PMID 6303843. doi:10.1016/0014-5793(82)80605-4.
- MacNeil DJ; Occi JL; Hey PJ; et al. (1994). „Cloning and expression of a human glucagon receptor.”. Biochem. Biophys. Res. Commun. 198 (1): 328—34. PMID 7507321. doi:10.1006/bbrc.1994.1046.
- Fujisawa T; Ikegami H; Yamato E; et al. (1995). „A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the association with diabetes mellitus.”. Diabetologia. 38 (8): 983—5. PMID 7589886. doi:10.1007/BF00400589.
- Unson CG, Macdonald D, Merrifield RB (1993). „The role of histidine-1 in glucagon action.”. Arch. Biochem. Biophys. 300 (2): 747—50. PMID 8382034. doi:10.1006/abbi.1993.1103.
- Chambers SM, Morris BJ (1996). „Glucagon receptor gene mutation in essential hypertension.”. Nat. Genet. 12 (2): 122. PMID 8563746. doi:10.1038/ng0296-122.
- Yamato E; Ikegami H; Takekawa K; et al. (1997). „Tissue-specific and glucose-dependent expression of receptor genes for glucagon and glucagon-like peptide-1 (GLP-1).”. Horm. Metab. Res. 29 (2): 56—9. PMID 9105899. doi:10.1055/s-2007-978985.
- Strazzullo P; Iacone R; Siani A; et al. (2001). „Altered renal sodium handling and hypertension in men carrying the glucagon receptor gene (Gly40Ser) variant.”. J. Mol. Med. 79 (10): 574—80. PMID 11692154. doi:10.1007/s001090100257.
- Shiota D; Kasamatsu T; Dib SA; et al. (2002). „Role of the Gly40Ser mutation in the glucagon receptor gene in Brazilian patients with type 2 diabetes mellitus.”. Pancreas. 24 (4): 386—90. PMID 11961492. doi:10.1097/00006676-200205000-00010.
- 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. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.
- Runge S; Gram C; Brauner-Osborne H; et al. (2003). „Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus.”. J. Biol. Chem. 278 (30): 28005—10. PMID 12724331. doi:10.1074/jbc.M301085200.
- Hassel S; Eichner A; Yakymovych M; et al. (2004). „Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry.”. Proteomics. 4 (5): 1346—58. PMID 15188402. doi:10.1002/pmic.200300770.
- 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. PMC 528928 . PMID 15489334. doi:10.1101/gr.2596504.
- Mortensen OH; Dichmann DS; Abrahamsen N; et al. (2007). „Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha.”. Gene. 393 (1-2): 127—36. PMID 17374560. doi:10.1016/j.gene.2007.01.023.