Journal ArticleDOI
The growth hormone receptor: mechanism of activation and clinical implications
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TLDR
A model in which the growth hormone receptor exists as a constitutive dimer is discussed in the light of salient information from closely related class 1 cytokine receptors, such as the erythropoietin, prolactin and thrombopOietin receptors.Abstract:
Growth hormone is widely used clinically to promote growth and anabolism and for other purposes. Its actions are mediated via the growth hormone receptor, both directly by tyrosine kinase activation and indirectly by induction of insulin-like growth factor 1 (IGF-1). Insensitivity to growth hormone (Laron syndrome) can result from mutations in the growth hormone receptor and can be treated with IGF-1. This treatment is, however, not fully effective owing to the loss of the direct actions of growth hormone and altered availability of exogenous IGF-1. Excessive activation of the growth hormone receptor by circulating growth hormone results in gigantism and acromegaly, whereas cell transformation and cancer can occur in response to autocrine activation of the receptor. Advances in understanding the mechanism of receptor activation have led to a model in which the growth hormone receptor exists as a constitutive dimer. Binding of the hormone realigns the subunits by rotation and closer apposition, resulting in juxtaposition of the catalytic domains of the associated tyrosine-protein kinase JAK2 below the cell membrane. This change results in activation of JAK2 by transphosphorylation, then phosphorylation of receptor tyrosines in the cytoplasmic domain, which enables binding of adaptor proteins, as well as direct phosphorylation of target proteins. This model is discussed in the light of salient information from closely related class 1 cytokine receptors, such as the erythropoietin, prolactin and thrombopoietin receptors.read more
Citations
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Journal ArticleDOI
Development and characterization of a novel GHR antibody antagonist, GF185.
TL;DR: It is shown that GF185 was able to neutralize growth hormone (GH) signalling and inhibit GH-induced Ba/F3-GHR proliferation and has a potential future application for the treatment of GH-dependent disease.
Journal ArticleDOI
Effect of quercetin on muscle growth and antioxidant status of the dark sleeper Odontobutis potamophila
TL;DR: The results showed that quercetin has no significant effects on the growth performance of O. potamophila, but is effective in increasing muscle growth rate and lowering muscle fat content.
Journal ArticleDOI
Enhanced Bioactivity of a Human GHR Antagonist Generated by Solid-Phase Site-Specific PEGylation.
Yue Wang,Ries J. Langley,Kyle Tamshen,Julia K. Harms,Martin Middleditch,Heather D. Maynard,Stephen M. F. Jamieson,Jo K. Perry +7 more
TL;DR: A novel PEGylated GHR antagonist is generated by the solid-phase site-specific attachment of mPEG maleimide at an introduced cysteine residue, which effectively reduces serum IGF-I in vivo.
Book ChapterDOI
Hypothalamic–Pituitary Regulation
TL;DR: The hypothalamic–pituitary unit transduces and amplifies central electrical and neurochemical signals and regulates peripheral hormonal regulatory homeostasis and acts to control pituitary and target gland responses with extensive positive and negative feedback mechanisms.
Dissertation
The roles of growth hormone and prolactin in the brain during development and recovery from hypoxic-ischemic injury
TL;DR: It is suggested that the manuscript should be rewritten in a more chapters-like style to better reflect the needs of the present and future generations of writers.
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Journal ArticleDOI
Human Growth Hormone and Extracellular Domain of Its Receptor: Crystal Structure of the Complex
TL;DR: Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor.
Journal ArticleDOI
Nuclear localization of EGF receptor and its potential new role as a transcription factor
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