Growth hormone signalling: sprouting links between pathways, human genetics and therapeutic options

Pilecka, Iwona; Whatmore, Andrew; Huijsduijnen, Rob Hooft van; Destenaves, Benoit; Clayton, Peter E.

doi:10.1016/j.tem.2006.11.004

Cited by 48 publications

(43 citation statements)

References 79 publications

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“…GH action is mediated through its binding to the GH receptor (GHR), a transmembrane protein that, upon ligand-induced dimerization, recruits intracellular JAK tyrosine kinases, specifically JAK2, which phosphorylate the GH receptor on tyrosine residues [15]. The phosphorylated GH receptor serves as a docking site for members of the signal transducer and activator of transcription (STAT) family, in particular STATs 1, 3, and 5, which are then tyrosine phosphorylated by the GHR-associated JAK kinase.…”

Section: The Gh-igf-i Axis In Modulating Growth and Organ Developmentmentioning

confidence: 99%

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

Mak

Cheung

Roberts

2008

Growth Hormone & IGF Research

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Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are important physiologic regulators of growth, body composition, and kidney function. Perturbations in the GH-IGF-I axis are responsible for many important complications seen in chronic kidney disease (CKD), such as growth retardation and cachectic wasting, as well as disease progression. Recent evidence suggests that CKD is characterized by abnormalities in GH and IGF-I signal transduction and the interaction of these pathways with those that involve other molecules such as ghrelin, myostatin, and the suppressor of cytokine signaling (SOCS) family. Further understanding of GH/IGF pathophysiology in CKD may lead to the development of therapeutic strategies for these devastating complications, which are associated with high rates of mortality and morbidity.

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Section: The Gh-igf-i Axis In Modulating Growth and Organ Developmentmentioning

confidence: 99%

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

Mak

Cheung

Roberts

2008

Growth Hormone & IGF Research

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“…GHR engagement triggers activation of Janus kinase 2 (JAK2), STAT-3 and -5, and the mitogen-activated phosphatase kinase pathways but is also under the control of negative feedback (1,2). Such feedback control includes ubiquitin-dependent endocytosis of the GHR (3,4), transcriptionally induced SOCS (suppressors of cytokine signaling) proteins, PIAS (protein inhibitors of activated STATs) and signaling attenuation by protein-tyrosine phosphatases (PTPs).…”

Section: Growth Hormone (Gh)mentioning

confidence: 99%

“…Such feedback control includes ubiquitin-dependent endocytosis of the GHR (3,4), transcriptionally induced SOCS (suppressors of cytokine signaling) proteins, PIAS (protein inhibitors of activated STATs) and signaling attenuation by protein-tyrosine phosphatases (PTPs). Of particular interest among these factors are the PTPs, enzymes that, if validated, constitute drugable targets that may be exploited to treat growth-related disorders (2). The human PTP family comprises 37 "classical" PTPs (which exclusively dephosphorylate phosphotyrosine residues) plus 65 "dual specific phosphatases," most of which in addition dephosphorylate serine-and threonine-phosphate residues (5).…”

Section: Growth Hormone (Gh)mentioning

confidence: 99%

Protein-tyrosine Phosphatase H1 Controls Growth Hormone Receptor Signaling and Systemic Growth

Pilecka

Patrignani

Pescini

et al. 2007

Journal of Biological Chemistry

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Several protein-tyrosine phosphatases (PTPs) have been implicated in the control of growth hormone receptor (GHR) signaling, but none have been shown to affect growth in vivo. We have applied a battery of molecular and cellular approaches to test a family-wide panel of PTPs for interference with GHR signaling. Among the subset of PTPs that showed activity in multiple readouts, we selected PTP-H1/PTPN3 for further in vivo studies and found that mice lacking the PTP-H1 catalytic domain show significantly enhanced growth over their wild type littermates. In addition, PTP-H1 mutant animals had enhanced plasma and liver mRNA expression of insulin-like growth factor 1, as well as increased bone density and mineral content. These observations point to a controlling role for PTP-H1 in modulating GHR signaling and systemic growth through insulin-like growth factor 1 secretion.

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“…7 GH binds growth hormone receptors (GHRs) located on the cell surface in order to activate the intracellular signaling pathways involved in these processes. 8 GH plays an important role in the growth of cartilage, and GHRs are especially present in the mandibular condyle, 9,10 which plays a significant role in the growth and development of craniofacial morphology by regulating the angle and size of the morphology. 7 Dysfunctional mutations in the GHR gene cause Laron syndrome (GH insensitivity syndrome), which is associated with characteristic craniofacial morphology and short stature.…”

Section: Introductionmentioning

confidence: 99%

Growth hormone receptor gene variant and three-dimensional mandibular morphology

Nakawaki

Yamaguchi

Isa

et al. 2016

The Angle Orthodontist

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Objective: To examine the relationship between three-dimensional mandibular morphology and growth hormone receptor (GHR) gene variants in a healthy Japanese population. Materials and Methods: The subjects, who were unrelated Japanese orthodontic patients, consisted of 64 men and 114 women. Using the Taqman genotyping assay, GHR gene rs6184 and rs6180 variants were detected in genomic DNA extracted from saliva. Mandibular volume and length were measured from cone-beam computed tomography images that were analyzed using Analyze image-processing software. The relationship between GHR gene variants and threedimensional mandibular morphology was statistically examined. Results: Statistical significance for the relationship between the distance between the left and right coronoid processes and rs6180 was noted (P , .05). Conclusion: Our results indicate that the GHR variant rs6180 is associated with the distance between the left and right coronoid process in the Japanese subjects. (Angle Orthod. 2017;87:68-73)

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Growth hormone signalling: sprouting links between pathways, human genetics and therapeutic options

Cited by 48 publications

References 79 publications

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

Protein-tyrosine Phosphatase H1 Controls Growth Hormone Receptor Signaling and Systemic Growth

Growth hormone receptor gene variant and three-dimensional mandibular morphology

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