This gene encodes a protein that is a transmembrane receptor for growth hormone. Binding of growth hormone to the receptor leads to reorientation of a pre-assembled receptor dimer dimerization (the receptor may however also exist as monomers on the cell surface ) 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. 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.
Conserved and variable positions of the GHR protein are evidenced by multiple amino acid sequence comparisons among rodents. The site in yellow emphasizes a Proline shared by all species in blue and represents a protein signature of their common ancestry.
^Brooks AJ, Waters MJ (September 2010). "The growth hormone receptor: mechanism of activation and clinical implications". Nature Reviews. Endocrinology. 6 (9): 515–25. doi:10.1038/nrendo.2010.123. PMID20664532.
^González L, Curto LM, Miquet JG, Bartke A, Turyn D, Sotelo AI (April 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 Hormone & IGF Research. 17 (2): 104–12. doi:10.1016/j.ghir.2006.12.002. PMID17321774.
^Brooks AJ, Dai W, O'Mara ML, Abankwa D, Chhabra Y, Pelekanos RA, Gardon O, Tunny KA, Blucher KM, Morton CJ, Parker MW, Sierecki E, Gambin Y, Gomez GA, Alexandrov K, Wilson IA, Doxastakis M, Mark AE, Waters MJ (May 2014). "Mechanism of activation of protein kinase JAK2 by the growth hormone receptor". Science. 344 (6185): 1249783. doi:10.1126/science.1249783. PMID24833397.
^Stofega MR, 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". Molecular Endocrinology. 14 (9): 1338–50. doi:10.1210/me.14.9.1338. PMID10976913.
^Moutoussamy S, Renaudie F, Lago F, Kelly PA, Finidori J (June 1998). "Grb10 identified as a potential regulator of growth hormone (GH) signaling by cloning of GH receptor target proteins". The Journal of Biological Chemistry. 273 (26): 15906–12. doi:10.1074/jbc.273.26.15906. PMID9632636.
^Frank SJ, Yi W, Zhao Y, Goldsmith JF, Gilliland G, Jiang J, Sakai I, Kraft AS (June 1995). "Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor". The Journal of Biological Chemistry. 270 (24): 14776–85. doi:10.1074/jbc.270.24.14776. PMID7540178.
^VanderKuur JA, Wang X, Zhang L, Campbell GS, 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". The Journal of Biological Chemistry. 269 (34): 21709–17. PMID8063815.
^Hellgren G, Jansson JO, Carlsson LM, Carlsson B (June 1999). "The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver". Growth Hormone & IGF Research. 9 (3): 212–8. doi:10.1054/ghir.1999.0111. PMID10502458.
^ abRam PA, Waxman DJ (December 1999). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". The Journal of Biological Chemistry. 274 (50): 35553–61. doi:10.1074/jbc.274.50.35553. PMID10585430.
^Adkins RM, Gelke EL, Rowe D, Honeycutt RL (May 2001). "Molecular phylogeny and divergence time estimates for major rodent groups: evidence from multiple genes". Molecular Biology and Evolution. 18 (5): 777–91. doi:10.1093/oxfordjournals.molbev.a003860. PMID11319262.
^Adkins RM, Walton AH, Honeycutt RL (March 2003). "Higher-level systematics of rodents and divergence time estimates based on two congruent nuclear genes". Molecular Phylogenetics and Evolution. 26 (3): 409–20. doi:10.1016/S1055-7903(02)00304-4. PMID12644400.
^Honeycutt RL, Rowe DL, Gallardo MH (March 2003). "Molecular systematics of the South American caviomorph rodents: relationships among species and genera in the family Octodontidae". Molecular Phylogenetics and Evolution. 26 (3): 476–89. doi:10.1016/S1055-7903(02)00368-8. PMID12644405.
^Steppan S, Adkins R, Anderson J (August 2004). "Phylogeny and divergence-date estimates of rapid radiations in muroid rodents based on multiple nuclear genes". Systematic Biology. 53 (4): 533–53. doi:10.1080/10635150490468701. PMID15371245.
^Rowe KC, Reno ML, Richmond DM, Adkins RM, Steppan SJ (April 2008). "Pliocene colonization and adaptive radiations in Australia and New Guinea (Sahul): multilocus systematics of the old endemic rodents (Muroidea: Murinae)". Molecular Phylogenetics and Evolution. 47 (1): 84–101. doi:10.1016/j.ympev.2008.01.001. PMID18313945.
^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.
^Fulton TL, Strobeck C (October 2006). "Molecular phylogeny of the Arctoidea (Carnivora): effect of missing data on supertree and supermatrix analyses of multiple gene data sets". Molecular Phylogenetics and Evolution. 41 (1): 165–81. doi:10.1016/j.ympev.2006.05.025. PMID16814570.
^Koepfli KP, Wayne RK (October 2003). "Type I STS markers are more informative than cytochrome B in phylogenetic reconstruction of the Mustelidae (Mammalia: Carnivora)". Systematic Biology. 52 (5): 571–93. doi:10.1080/10635150390235368. PMID14530127.
^Koepfli KP, Jenks SM, Eizirik E, Zahirpour T, Van Valkenburgh B, Wayne RK (March 2006). "Molecular systematics of the Hyaenidae: relationships of a relictual lineage resolved by a molecular supermatrix". Molecular Phylogenetics and Evolution. 38 (3): 603–20. doi:10.1016/j.ympev.2005.10.017. PMID16503281.