ArticleProceedings of the National Academy of Sciences of the United States of America1995
A single arginine residue determines species specificity of the human growth hormone receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 76 citations in OpenAlex.
- Development of human growth hormone-treated chimeric mice with humanized livers for an evaluation model of drug-induced fatty liver disease.Archives of toxicology · 2025Article
- Molecular Cloning, Expression, Sequence Characterization and Structural Insight of Bubalus bubalis Growth Hormone-Receptor.Molecular biotechnology · 2023Article
- The growth of xenotransplanted hearts can be reduced with growth hormone receptor knockout pig donors.The Journal of thoracic and cardiovascular surgery · 2023Article
- GH Action in Prostate Cancer Cells Promotes Proliferation, Limits Apoptosis, and Regulates Cancer-related Gene Expression.Endocrinology · 2022Article
- Physiological aspects of pig kidney xenotransplantation and implications for management following transplant.Xenotransplantation · 2022Review
- Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers.Biomedicines · 2021Article
- Human Growth and Growth Hormone: From Antiquity to the Recominant Age to the Future.Frontiers in endocrinology · 2021Review
- Growth hormone - past, present and future.Nature reviews. Endocrinology · 2018Review
- A growth hormone receptor SNP promotes lung cancer by impairment of SOCS2-mediated degradation.Oncogene · 2018Article
- The forgotten lactogenic activity of growth hormone: important implications for rodent studies.Endocrinology · 2015Article
- Serum IGF-1 is insufficient to restore skeletal size in the total absence of the growth hormone receptor.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2013Article
- Genetic and structural characterization of the growth hormone gene and protein from tench, Tinca tinca.Fish physiology and biochemistry · 2012Article
- Abrogation of growth hormone secretion rescues fatty liver in mice with hepatocyte-specific deletion of JAK2.The Journal of clinical investigation · 2011Article
- Aqueous humor rapidly stimulates myocilin secretion from human trabecular meshwork cells.Experimental eye research · 2010Article
- Forced unbinding of GPR17 ligands from wild type and R255I mutant receptor models through a computational approach.BMC structural biology · 2010Article
- Evolution of receptors for growth hormone and somatolactin in fish and land vertebrates: lessons from the lungfish and sturgeon orthologues.Journal of molecular evolution · 2007Article
- Energetic analysis of an antigen/antibody interface: alanine scanning mutagenesis and double mutant cycles on the HyHEL-10/lysozyme interaction.Protein science : a publication of the Protein Society · 1999Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Although growth hormone (GH) receptors (GHRs) in many species bind human (h) GH as well as their own GH, the hGHR only binds primate GH. Arg43 in hGHR interacts with Asp171 of hGH. Nonprimates have a His in the position equivalent to residue 171 of primate GH and a Leu in position 43 of primate GHR. To determine whether Arg43 accounts for the species specificity of the hGHR, point mutations that changed Leu43 to Arg were introduced into the cDNAs encoding the bovine (b) GHR or the rat GH binding protein (GHBP) and these mutants or their wild-type (WT) counterparts were expressed in mouse L cells. Binding of hGH or bGH to transfected cells or to GHBP secreted into the incubation medium was assessed by displacement of 125I-labeled hGH. WT and mutant bGHR bound hGH with similar affinity, but the affinity of the mutant receptors for bGH was reduced 200-fold. Likewise, WT and mutant GHBP bound hGH with equal affinity, but only WT GHBP bound bGH. Cross-linking of 125I-labeled hGH to WT or mutant GHR produced a 141-kDa labeled complex whose appearance was blocked by unlabeled hGH, but bGH blocked cross-linking only to WT receptors. Both hGH and bGH stimulated tyrosine phosphorylation of a 95-kDa protein in cells transfected with WT GHR, but bGH was less effective in cells expressing mutant GHR. We conclude that incompatibility of Arg43 in the hGHR with His171 in nonprimate GH is the major determinant of species specificity.
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