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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Pituitary Hormones and Orofacial Pain.
TL;DR: Understanding the involvement of pituitary hormones in orofacial pain, especially sex-dependent aspects of such pain, is essential to both optimize current therapies as well as provide novel and sex-specific pharmacology for a diversity of associated conditions.
Journal ArticleDOI
Focus on growth hormone deficiency and bone in adults.
TL;DR: Retrospective and prospective data suggest that GH replacement is associated with decreased fracture risk in adults, however, data from randomized clinical trials are lacking and potentially confounding the interpretation of densitometric data.
Journal ArticleDOI
A Human Variant of Glucose-Regulated Protein 94 That Inefficiently Supports IGF Production
Michal Marzec,Colin P. Hawkes,Davide Eletto,Sarah Boyle,Ron G. Rosenfeld,Vivian Hwa,Jan M. Wit,Hermine A. van Duyvenvoorde,Wilma Oostdijk,Monique Losekoot,Oluf Pedersen,Bu B. Yeap,Leon Flicker,Nir Barzilai,Gil Atzmon,Adda Grimberg,Yair Argon +16 more
TL;DR: In vitro data strongly support a causal relationship between the GRP94 variant and the decreased concentration of circulating IGF-1, as observed in human carriers of P300L, and represent a novel causal genetic mechanism that limits IGF biosynthesis.
Review Article BMP9 signaling in stem cell differentiation and osteogenesis
Joseph D. Lamplot,Jiaqiang Qin,Guoxin Nan,Jinhua Wang,Xing Liu,Liangjun Yin,Justin Tomal,Ruidong Li,Wei Shui,Hongyu Zhang,Stephanie H. Kim,Wenwen Zhang,Jiye Zhang,Sahitya K. Denduluri,Mary Rose Rogers,Abdullah Pratt,Rex C. Haydon,Hue H. Luu,Lewis L. Shi,Tong-Chuan He,Chongqing Key Labora +20 more
TL;DR: Current knowledge of BMP9-mediated osteogenesis is summarized by presenting recently completed work which may help to further elucidate these pathways, which are known to be a potent osteogenic factor but relatively little is known about the specific mechanisms responsible for these effects.
Journal ArticleDOI
An international ecological study of adult height in relation to cancer incidence for 24 anatomical sites
TL;DR: Incidence of cancer was associated with tallness in the majority of anatomical/cancer sites investigated, and the underlying biological mechanisms are unclear, but may include nutrition and early-life exposure to hormones.
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.
Journal ArticleDOI
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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