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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Mineralocorticoid receptor suppresses cancer progression and the Warburg effect by modulating the miR‐338‐3p‐PKLR axis in hepatocellular carcinoma
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The effects of growth hormone on adipose tissue: old observations, new mechanisms.
John J. Kopchick,John J. Kopchick,Darlene E. Berryman,Darlene E. Berryman,Vishwajeet Puri,Kevin Y. Lee,Jens Otto Lunde Jørgensen +6 more
TL;DR: This Review provides an up-to-date overview of the lipolytic effects of growth hormone (GH) in humans, mice and cultured cells and explains lipolysis in terms of GH-induced intracellular signalling and its effect on obesity, insulin resistance and lipotoxicity.
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Autocrine/Paracrine Human Growth Hormone-stimulated MicroRNA 96-182-183 Cluster Promotes Epithelial-Mesenchymal Transition and Invasion in Breast Cancer.
Weijie Zhang,Pengxu Qian,Xiao Zhang,Min Zhang,Hong Wang,Mingming Wu,Xiangjun Kong,Sheng Tan,Keshuo Ding,Jo K. Perry,Zhengsheng Wu,Yuan Cao,Peter E. Lobie,Tao Zhu +13 more
TL;DR: A novel hGH-GHR-STAT3/STAT5-miR-96-182-183-BRMS1L-ZEB1/E47-EMT/invasion axis is elucidated, which provides further understanding of the mechanism of autocrine/paracrine h GH-stimulated EMT and invasion in breast cancer.
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Giant tortoise genomes provide insights into longevity and age-related disease
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TL;DR: The genomes of two long-lived giant tortoises, including Lonesome George, reveal candidate genes and pathways associated with their development, gigantism and longevity and expands the understanding of the genomic determinants of ageing.
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Low incidence of pathology detection and high cost of screening in the evaluation of asymptomatic short children
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References
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Journal ArticleDOI
Systematic Review: Process of Forming Academic Service Partnerships to Reform Clinical Education
TL;DR: This study’s findings can provide practical guidelines to steer partnership programs within the academic and clinical bodies, with the aim of providing a collaborative partnership approach to clinical education.
Journal ArticleDOI
Handbook of Physiology.
TL;DR: This is the first volume of the proposed many-sectioned "Handbook" in which the American Physiological Society intends to present comprehensively the entire field of physiology.
Journal ArticleDOI
A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
Robert Kralovics,Francesco Passamonti,Andreas Buser,Soon Siong Teo,Ralph Tiedt,Jakob Passweg,André Tichelli,Mario Cazzola,Radek C. Skoda +8 more
TL;DR: Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages and a high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2.
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.
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Nuclear localization of EGF receptor and its potential new role as a transcription factor
Shiaw Yih Lin,Keishi Makino,Weiya Xia,Angabin Matin,Yong Wen,Ka Yin Kwong,Lilly Y.W. Bourguignon,Mien Chie Hung +7 more
TL;DR: It is demonstrated that nuclear EGFR is strongly correlated with highly proliferating activities of tissues and associated with promoter region of cyclin D1 in vivo, suggesting that EGFR might function as a transcription factor to activate genes required for highly proliferationating activities.
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