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
Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes
Gitte W. Haxholm,Louise F. Nikolajsen,Johan G. Olsen,Jacob Fredsted,Flemming H. Larsen,Vincent Goffin,Stine F. Pedersen,Andrew J. Brooks,Michael J. Waters,Birthe B. Kragelund +9 more
TL;DR: The present study provides the first comprehensive structural characterization of any cytokine receptor ICD and demonstrates that the human prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) ICDs are intrinsically disordered throughout their entire lengths.
Journal ArticleDOI
Single-base resolution of mouse offspring brain methylome reveals epigenome modifications caused by gestational folic acid.
TL;DR: It is demonstrated that high maternal FA during gestation induces substantial alteration in methylation pattern and gene expression of several genes in the cerebral hemispheres of the offspring, and such changes may influence the overall development.
Journal ArticleDOI
The wonders of BMP9: From mesenchymal stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism to regenerative medicine.
Sami Mostafa,Mikhail Pakvasa,Elam Coalson,Allen Zhu,Alex Alverdy,Alex Alverdy,Hector Castillo,Jiaming Fan,Alex Li,Yixiao Feng,Di Wu,Elliott Bishop,Scott Du,Mia Spezia,Alissa N. Li,Ofir Hagag,Alison Deng,Winny Liu,Mingyang Li,Sherwin S. W. Ho,Aravind Athiviraham,Michael J. Lee,Jennifer Moriatis Wolf,Guillermo A. Ameer,Hue H. Luu,Rex C. Haydon,Jason Strelzow,Kelly Hynes,Tong-Chuan He,Russell R. Reid +29 more
TL;DR: Emerging evidence indicates that, besides its osteogenic activity, BMP9 exerts a broad range of biological functions, including stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism.
Journal ArticleDOI
Mechanisms in endocrinology: regulation of glucose metabolism by the ghrelin system: multiple players and multiple actions.
Kristy M. Heppner,Jenny Tong +1 more
TL;DR: In this paper, the authors discuss the current literature on the gluco-regulatory action of the ghrelin system (dAG, AG, GHSR, and GOAT) with specific emphasis aimed toward distinguishing AG vs dAG action.
Journal ArticleDOI
The Impact of Adipose Tissue on Insulin Resistance in Acromegaly
TL;DR: Recent data suggesting that AT inflammation, altered AT distribution, and impaired adipogenesis are potential mechanisms contributing to systemic insulin resistance in acromegaly are discussed.
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Nuclear localization of EGF receptor and its potential new role as a transcription factor
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