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
Cysteine induces longitudinal bone growth in mice by upregulating IGF-I.
TL;DR: The data suggest that Cys may have potential for use as a growth-promoting agent and increases the thickness of growth plates through the upregulation of IGF-I, which results from the phosphorylation of JAK2-STAT5.
Journal ArticleDOI
Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children
Ralph Decker,Anders O.H. Nygren,Berit Kriström,Andreas F M Nierop,Jan Gustafsson,Kerstin Albertsson-Wikland,Jovanna Dahlgren +6 more
TL;DR: Dose-dependent thresholds were observed for different GH effects, with cardiac tissue being the most responsive and level of IGF-I the least responsive, with the threshold effect for height in the interval between.
Journal ArticleDOI
Identifying growth hormone-regulated enhancers in the Igf1 locus.
TL;DR: Mechanisms of regulation of IGF-I gene transcription by GH are addressed by generating cell lines in which the rat Igf1 chromosomal locus has been incorporated into the mouse genome, and physiological levels of GH rapidly and potently activate Ig f1 gene transcription while stimulating physical interactions in chromatin between inducible Stat5b-binding elements and the Igf 1 promoters.
Journal ArticleDOI
Effects of growth hormone therapeutic supplementation on hematopoietic stem/progenitor cells in children with growth hormone deficiency: focus on proliferation and differentiation capabilities
Miłosz P. Kawa,Iwona Stecewicz,Katarzyna Piecyk,Ewa Pius-Sadowska,Edyta Paczkowska,Dorota Rogińska,Anna Sobuś,Karolina Łuczkowska,Elzbieta Gawrych,Elżbieta Petriczko,Mieczysław Walczak,Bogusław Machaliński +11 more
TL;DR: Molecular mechanisms by which GH influences hematopoiesis might provide a basis for designing therapeutic interventions for hematological complications related to GHD.
Journal ArticleDOI
Anti-idiotypic antibody: A new strategy for the development of a growth hormone receptor antagonist.
TL;DR: The current findings suggest that anti-idiotypic antibody may represent a novel strategy to produce a new class of growth hormone receptor antagonist, and this strategy may be applied with other cytokines or growth factors.
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Nuclear localization of EGF receptor and its potential new role as a transcription factor
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