Growth hormone receptor

Growth hormone receptor

PDB rendering based on 1a22.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GHR ; GHBP; GHIP
External IDs OMIM: 600946 MGI: 95708 HomoloGene: 134 ChEMBL: 1976 GeneCards: GHR Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 2690 14600
Ensembl ENSG00000112964 ENSMUSG00000055737
UniProt P10912 P16882
RefSeq (mRNA) NM_000163 NM_001048147
RefSeq (protein) NP_000154 NP_001041643
Location (UCSC) Chr 5:
42.42 – 42.72 Mb		 Chr 15:
3.32 – 3.58 Mb
PubMed search

Growth hormone receptor is a protein that in humans is encoded by the GHR gene.[1] GHR orthologs [2] have been identified in most mammals.

This gene encodes a protein that is a transmembrane receptor for growth hormone. Binding of growth hormone to the receptor leads to receptor dimerization (the receptor may however also exist as a pre-assembled non-functional dimer [3]) and the activation of an intra- and intercellular signal transduction pathway leading to growth. A common alternate allele of this gene, called GHRd3, lacks exon three and has been well-characterized. Mutations in this gene have been associated with Laron syndrome, also known as the growth hormone insensitivity syndrome (GHIS), a disorder characterized by short stature (proportional dwarfism). Other splice variants, including one encoding a soluble form of the protein (GHRtr), have been observed but have not been thoroughly characterized.[1] Laron mice (that is mice genetically engineered to carry defective Ghr), have a dramatic reduction in body mass (only reaching 50% of the weight of normal siblings), and also show a ~40% increase in lifespan.

Interactions

Growth hormone receptor has been shown to interact with SGTA,[4] PTPN11,[5][6] Janus kinase 2,[7][8][9] Suppressor of cytokine signaling 1[10] and CISH.[10]

Evolution

The GHR gene is used in animals as a nuclear DNA phylogenetic marker.[2] The exon 10 has first been experienced to explore the phylogeny of the major groups of Rodentia.[11][12][13] GHR has also proven useful at lower taxonomic levels, e.g., in octodontoid,[14] arvicoline,[15] muroid,[16][17] murine,[18] and peromyscine [19] rodents, in arctoid [20] and felid [21] carnivores, and in dermopterans.[22] Note that the GHR intron 9 has also been used to investigate the mustelid [23] and hyaenid [24] carnivores phylogenetics.

Antagonists

Growth hormone receptor antagonists such as pegvisomant (trade name Somavert) are used in the treatment of acromegaly.[25] They are used if the tumor of the pituitary gland causing the acromegaly cannot be controlled with surgery or radiation, and the use of somatostatin analogues is unsuccessful. Pegvisomant is delivered as a powder that is mixed with water and injected under the skin.[26]

References

  1. 1 2 "Entrez Gene: GHR growth hormone receptor".
  2. 1 2 "OrthoMaM phylogenetic marker: GHR coding sequence".
  3. ↑ Gonzalez, L., L. M. Curto, et al. (2007). "Differential regulation of membrane associated-growth hormone binding protein (MA-GHBP) and growth hormone receptor (GHR) expression by growth hormone (GH) in mouse liver." Growth Horm IGF Res 17(2): 104-112.
  4. ↑ Schantl, Julia A; Roza Marcel; De Jong Ad P; Strous Ger J (August 2003). "Small glutamine-rich tetratricopeptide repeat-containing protein (SGT) interacts with the ubiquitin-dependent endocytosis (UbE) motif of the growth hormone receptor". Biochem. J. (England) 373 (Pt 3): 855–63. doi:10.1042/BJ20021591. ISSN 0264-6021. PMC 1223544. PMID 12735788.
  5. ↑ Stofega, M R; Herrington J; Billestrup N; Carter-Su C (September 2000). "Mutation of the SHP-2 binding site in growth hormone (GH) receptor prolongs GH-promoted tyrosyl phosphorylation of GH receptor, JAK2, and STAT5B". Mol. Endocrinol. (UNITED STATES) 14 (9): 1338–50. doi:10.1210/me.14.9.1338. ISSN 0888-8809. PMID 10976913.
  6. ↑ Moutoussamy, S; Renaudie F; Lago F; Kelly P A; Finidori J (June 1998). "Grb10 identified as a potential regulator of growth hormone (GH) signaling by cloning of GH receptor target proteins". J. Biol. Chem. (UNITED STATES) 273 (26): 15906–12. doi:10.1074/jbc.273.26.15906. ISSN 0021-9258. PMID 9632636.
  7. ↑ Frank, S J; Yi W; Zhao Y; Goldsmith J F; Gilliland G; Jiang J; Sakai I; Kraft A S (June 1995). "Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor". J. Biol. Chem. (UNITED STATES) 270 (24): 14776–85. doi:10.1074/jbc.270.24.14776. ISSN 0021-9258. PMID 7540178.
  8. ↑ VanderKuur, J A; Wang X; Zhang L; Campbell G S; Allevato G; Billestrup N; Norstedt G; Carter-Su C (August 1994). "Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase". J. Biol. Chem. (UNITED STATES) 269 (34): 21709–17. ISSN 0021-9258. PMID 8063815.
  9. ↑ Hellgren, G; Jansson J O; Carlsson L M; Carlsson B (June 1999). "The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver". Growth Horm. IGF Res. (SCOTLAND) 9 (3): 212–8. doi:10.1054/ghir.1999.0111. ISSN 1096-6374. PMID 10502458.
  10. 1 2 Ram, P A; Waxman D J (December 1999). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". J. Biol. Chem. (UNITED STATES) 274 (50): 35553–61. doi:10.1074/jbc.274.50.35553. ISSN 0021-9258. PMID 10585430.
  11. ↑ Adkins RM, Gelke EL, Rowe D, Honeycutt RL (2001). "Molecular phylogeny and divergence time estimates for major rodent groups: evidence from multiple genes.". Mol Biol Evol 18 (5): 777–791. doi:10.1093/oxfordjournals.molbev.a003860. PMID 11319262.
  12. ↑ Adkins R. M., Walton A. H. & Honeycutt R. L. (2003). "Higher-level systematics of rodents and divergence time estimates based on two congruent nuclear genes". Mol. Phylogenet. Evol. 26 (3): 409–420. doi:10.1016/S1055-7903(02)00304-4. PMID 12644400.
  13. ↑ Blanga-Kanfi S., Miranda H., Penn O., Pupko T., DeBry R. W. & Huchon D. (2009). "Rodent phylogeny revised: analysis of six nuclear genes from all major rodent clades". BMC Evol. Biol. 9: 71. doi:10.1186/1471-2148-9-71. PMC 2674048. PMID 19341461.
  14. ↑ Honeycutt R. L., Rowe D. L. & Gallardo M. H. (2003). "Molecular systematics of the South American caviomorph rodents: relationships among species and genera in the family Octodontidae". Mol. Phylogenet. Evol. 26 (3): 476–489. doi:10.1016/S1055-7903(02)00368-8. PMID 12644405.
  15. ↑ Galewski T., Tilak M., Sanchez S., Chevret P., Paradis E. & Douzery E. J. P. (2006). "The evolutionary radiation of Arvicolinae rodents (voles and lemmings): relative contribution of nuclear and mitochondrial DNA phylogenies". BMC Evol. Biol. 6: 80. doi:10.1186/1471-2148-6-80. PMC 1618403. PMID 17029633.
  16. ↑ Steppan S. J., Adkins R. M. & Anderson J. (2004). "Phylogeny and divergence-date estimates of rapid radiations in muroid rodents based on multiple nuclear genes". Syst. Biol. 53 (4): 533–553. doi:10.1080/10635150490468701. PMID 15371245.
  17. ↑ Rowe K. C., Reno M. L., Richmond D. M., Adkins R. M. & Steppan S. J. (2008). "Pliocene colonization and adaptive radiations in Australia and New Guinea (Sahul): multilocus systematics of the old endemic rodents (Muroidea: Murinae)". Mol. Phylogenet. Evol. 47 (1): 84–101. doi:10.1016/j.ympev.2008.01.001. PMID 18313945.
  18. ↑ Lecompte E., Aplin K., Denys C., Catzeflis F., Chades M. & Chevret P. (2008). "Phylogeny and biogeography of African Murinae based on mitochondrial and nuclear gene sequences, with a new tribal classification of the subfamily". BMC Evol. Biol. 8: 199. doi:10.1186/1471-2148-8-199. PMC 2490707. PMID 18616808.
  19. ↑ Miller J. R. & Engstrom M. D. (2008). "The relationships of major lineages within peromyscine rodents: a molecular phylogenetic hypothesis and systematic reappraisal". J. Mammal. 89 (5): 1279–1295. doi:10.1644/07-MAMM-A-195.1.
  20. ↑ Fulton T. L. & Strobeck C. (2006). "Molecular phylogeny of the Arctoidea (Carnivora): effect of missing data on supertree and supermatrix analyses of multiple gene data sets". Mol. Phylogenet. Evol. 41 (1): 165–181. doi:10.1016/j.ympev.2006.05.025. PMID 16814570.
  21. ↑ Johnson W. E., Eizirik E., Pecon-Slattery J., Murphy W. J., Antunes A., Teeling E. & O'Brien S. J. (2006). "The late Miocene radiation of modern Felidae: a genetic assessment". Science 311 (5757): 73–77. doi:10.1126/science.1122277. PMID 16400146.
  22. ↑ Janecka J. E., Helgen K. M., Lim N. T., Baba M., Izawa M., Boeadi & Murphy W. J. (2008). "Evidence for multiple species of Sunda colugo". Curr. Biol. 18 (21): R1001–R1002. doi:10.1016/j.cub.2008.09.005. PMID 19000793.
  23. ↑ Koepfli K. P. & Wayne R. K. (2003). "Type I STS markers are more informative than cytochrome B in phylogenetic reconstruction of the Mustelidae (Mammalia: Carnivora)". Syst. Biol. 52 (5): 571–593. doi:10.1080/10635150390235368. PMID 14530127.
  24. ↑ Koepfli K. P., Jenks S. M., Eizirik E., Zahirpour T., Van Valkenburgh B. & Wayne R. K. (2006). "Molecular systematics of the Hyaenidae: relationships of a relictual lineage resolved by a molecular supermatrix". Mol. Phylogenet. Evol. 38 (3): 603–620. doi:10.1016/j.ympev.2005.10.017. PMID 16503281.
  25. ↑ Schreiber, I; Buchfelder M; Droste M; et al. (January 2007). "Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant Observational Study". European Journal of Endocrinology 156 (1): 75–82. doi:10.1530/eje.1.02312. PMID 17218728.
  26. ↑ "Scientific Discussion of Somavert" (PDF). European Medicines Agency. 2004.

External links

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