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 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 engeneered to not 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,[3] PTPN11,[4][5] Janus kinase 2,[6][7][8] Suppressor of cytokine signaling 1[9] and CISH.[9]
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 [10][11][12]. GHR has also proven useful at lower taxonomic levels, e.g., in octodontoid [13], arvicoline [14], muroid [15][16], murine [17], and peromyscine [18] rodents, in arctoid [19] and felid [20] carnivores, and in dermopterans [21]. Note that the GHR intron 9 has also been used to investigate the mustelid [22] and hyaenid [23] carnivores phylogenetics.
References
- ^ a b "Entrez Gene: GHR growth hormone receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2690.
- ^ a b "OrthoMaM phylogenetic marker: GHR coding sequence". http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000112964_GHR.xml.
- ^ Schantl, Julia A; Roza Marcel, De Jong Ad P, Strous Ger J (Aug. 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. PMID 12735788.
- ^ Stofega, M R; Herrington J, Billestrup N, Carter-Su C (Sep. 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. ISSN 0888-8809. PMID 10976913.
- ^ Moutoussamy, S; Renaudie F, Lago F, Kelly P A, Finidori J (Jun. 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. ISSN 0021-9258. PMID 9632636.
- ^ Frank, S J; Yi W, Zhao Y, Goldsmith J F, Gilliland G, Jiang J, Sakai I, Kraft A S (Jun. 1995). "Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor". J. Biol. Chem. (UNITED STATES) 270 (24): 14776-85. ISSN 0021-9258. PMID 7540178.
- ^ VanderKuur, J A; Wang X, Zhang L, Campbell G S, Allevato G, Billestrup N, Norstedt G, Carter-Su C (Aug. 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.
- ^ Hellgren, G; Jansson J O, Carlsson L M, Carlsson B (Jun. 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.
- ^ a b Ram, P A; Waxman D J (Dec. 1999). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". J. Biol. Chem. (UNITED STATES) 274 (50): 35553-61. ISSN 0021-9258. PMID 10585430.
- ^ 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. PMID 11319262.
- ^ 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: 409-420. PMID 12644400.
- ^ 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. PMID 19341461. http://www.biomedcentral.com/1471-2148/9/71.
- ^ 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. PMID 12644405.
- ^ 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. PMID 17029633. http://www.biomedcentral.com/1471-2148/6/80.
- ^ 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. PMID 15371245.
- ^ 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. PMID 18313945.
- ^ 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. PMID 18616808. http://www.biomedcentral.com/1471-2148/8/199/.
- ^ 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.
- ^ 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. PMID 16814570.
- ^ 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. PMID 16400146.
- ^ 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. PMID 19000793.
- ^ 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. PMID 14530127.
- ^ 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. PMID 16503281.
External links
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1a22: HUMAN GROWTH HORMONE BOUND TO SINGLE RECEPTOR
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1axi: STRUCTURAL PLASTICITY AT THE HGH:HGHBP INTERFACE
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1hwg: 1:2 COMPLEX OF HUMAN GROWTH HORMONE WITH ITS SOLUBLE BINDING PROTEIN
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1hwh: 1:1 COMPLEX OF HUMAN GROWTH HORMONE MUTANT G120R WITH ITS SOLUBLE BINDING PROTEIN
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1kf9: PHAGE DISPLAY DERIVED VARIANT OF HUMAN GROWTH HORMONE COMPLEXED WITH TWO COPIES OF THE EXTRACELLULAR DOMAIN OF ITS RECEPTOR
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2aew: A model for growth hormone receptor activation based on subunit rotation within a receptor dimer
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3hhr: HUMAN GROWTH HORMONE AND EXTRACELLULAR DOMAIN OF ITS RECEPTOR: CRYSTAL STRUCTURE OF THE COMPLEX
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