Regulation of growth hormone induced JAK2 and mTOR signalling by hepatic protein tyrosine phosphatase 1B

Owen, Carl; Lees, Emma K.; Mody, Nimesh; Delibegović, Mirela

doi:10.1016/j.diabet.2014.02.008

Cited by 15 publications

(3 citation statements)

References 14 publications

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“…The same authors showed that PTP-1B KO mice were characterized by the increased STAT5β phosphorylation and, in consequence, the increased level of the IGF-1 in liver was stated. Also Owen et al [ 108 ] planned a study to investigate the role of PTP-1B in GH signal transduction in the liver. This team conducted an experiment on mice with the local deletion of the gene coding PTP-1B protein (liver-specific PTP-1B −/− ) and compared the impact of standard and high-fat diets.…”

Section: Ghr-jak2-stat Inhibitorsmentioning

confidence: 99%

Post-Receptor Inhibitors of the GHR-JAK2-STAT Pathway in the Growth Hormone Signal Transduction

Wójcik

Krawczyńska

Antushevich

et al. 2018

IJMS

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The growth hormone (GH) plays a key role in the regulation of metabolic processes in an organism. Determination of the correct structure and functioning of the growth hormone receptor (GHR) allowed for a more detailed research of its post-receptor regulators, which substantially influences its signal transduction. This review is focused on the description of the post-receptor inhibitors of the GHR-JAK2-STAT pathway, which is one of the most important pathways in the transduction of the somatotropic axis signal. The aim of this review is the short characterization of the main post-receptor inhibitors, such as: cytokine-inducible SH2-containing protein (CIS), Suppressors of Cytokine Signaling (SOCS) 1, 2 and 3, sirtuin 1 (SIRT1), protein inhibitors of activated STAT (PIAS) 1, 3 and PIAS4, protein tyrosine phosphatases (PTP) 1B and H1, Src homology 2 (SH2) domain containing protein tyrosine phosphatase (SHP) 1, 2 and signal regulatory protein (SIRP) α1. The equilibrium between these regulators activity and inhibition is of special concern because, as many studies showed, even slight imbalance may disrupt the GH activity causing serious diseases. The regulation of the described inhibitors expression and activity may be a point of interest for pharmaceutical industry.

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Section: Ghr-jak2-stat Inhibitorsmentioning

confidence: 99%

Post-Receptor Inhibitors of the GHR-JAK2-STAT Pathway in the Growth Hormone Signal Transduction

Wójcik

Krawczyńska

Antushevich

et al. 2018

IJMS

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“…However, the fact that IGF-I levels remain significantly lower in individuals with NAFLD after corrections for weight, waist circumference, and diabetes ( 25 ) suggests that their livers are resistant to the actions of GH. In fact, mice made obese by high-fat feeding fail to respond to an acute injection of GH by increasing the level of hepatic pStat5b ( 26 ), where the GHR/Jak2/Stat5b signal transduction pathway is required for GH-mediated regulation of IGF-I gene expression ( 27 ). In addition, rats fed a high-fat, low-carbohydrate diet exhibited a decrease in hepatic expression of the GHR (mRNA and protein), pStat5b protein, and IGF-I mRNA levels ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice

et al. 2015

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Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have low growth hormone (GH) production and/or hepatic GH resistance. GH replacement can resolve the fatty liver condition in diet-induced obese rodents and in GH-deficient patients. However, it remains to be determined whether this inhibitory action of GH is due to direct regulation of hepatic lipid metabolism. Therefore, an adult-onset, hepatocyte-specific, GH receptor (GHR) knockdown (aLivGHRkd) mouse was developed to model hepatic GH resistance in humans that may occur after sexual maturation. Just 7 days after aLivGHRkd, hepatic de novo lipogenesis (DNL) was increased in male and female chow-fed mice, compared with GHR-intact littermate controls. However, hepatosteatosis developed only in male and ovariectomized female aLivGHRkd mice. The increase in DNL observed in aLivGHRkd mice was not associated with hyperactivation of the pathway by which insulin is classically considered to regulate DNL. However, glucokinase mRNA and protein levels as well as fructose-2,6-bisphosphate levels were increased in aLivGHRkd mice, suggesting that enhanced glycolysis drives DNL in the GH-resistant liver. These results demonstrate that hepatic GH actions normally serve to inhibit DNL, where loss of this inhibitory signal may explain, in part, the inappropriate increase in hepatic DNL observed in NAFLD patients.

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“…Relevant in wild-type fasted mice, the GH resistance state develops, which is manifested by disorders in somatotropic axis at the GHR level, whereas in fasted PTP-1B KO mice, despite starvation, GH resistance state does not develop. PTP-1B KO mice are characterized by increased STAT5b tyrosine phosphorylation and augmented level of IGF-1 [87,88]. The PTP known as Src homology 2 (SH2) containing protein tyrosine phosphatase (SHP-1) was initially described in the hematopoietic system [89].…”

Section: Protein Phosphatases and Signal Regulatory Proteins (Sirps)mentioning

confidence: 99%

Control of Liver Gene Expression by Sex Steroids and Growth Hormone Interplay

Fernández-Pérez¹,

Mirecki-Garrido²,

Recio³

et al. 2020

Chemistry and Biological Activity of Steroids

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Sex steroids have important physiological actions, which are not limited to reproductive organs, in both females and males. They exert important physiological roles, including the regulation of somatotropic-liver axis, intermediate metabolism, or gender dimorphism. This is in part because the liver is a sex steroid-responsive organ where sex steroid-and growth hormone (GH)-dependent signaling pathways connect to regulate complex gene expression networks. Sex steroids can impact liver gene expression by a direct, through hepatic estrogen receptor (ER)α and androgen receptor (AR), or indirect mechanisms, by modulation of pituitary GH secretion and/or interaction with the GHR-STAT5b signaling pathway. Therefore, deficiency of sex steroid-and GH-dependent signaling pathways might cause a dramatic impact on mammalian liver physiology. In this chapter, we will focus our attention on main concepts and paradigms involved in the role and interplay between sex steroid-and GH-dependent signaling to regulate gene expression networks in the mammalian liver. A better understanding of how sex steroids and interactions with GH-STAT5b signaling pathway influence physiological and pathological states in the liver will contribute to improve clinical management of patients with disorders in body growth, development, and metabolism.Chemistry and Biological Activity of Steroids 2 androgen/AR [6,7,[21][22][23][24][25] or signaling pathways in adults causes a similar metabolic-like syndrome (i.e., fatty liver, adiposity, insulin resistance), a phenotype that might be ameliorated by E2/T or GH replacement. Therefore, the interplay between sex steroids and GH is clinically relevant because of its importance in the regulation of endocrine, metabolic, and gender-differentiated actions on the mammalian liver [33]. A better understanding of this complex sex steroid-GH interplay in physiological and pathological states will contribute to prevent health damage and improve clinical management of patients with growth, developmental, and metabolic disorders. In this review, we will summarize the role of sex steroid-and GH-dependent signaling pathways on liver gene expression. The liver is as sex steroid-responsive organSex steroids can regulate liver gene transcription through direct and indirect mechanisms.

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Regulation of growth hormone induced JAK2 and mTOR signalling by hepatic protein tyrosine phosphatase 1B

Cited by 15 publications

References 14 publications

Post-Receptor Inhibitors of the GHR-JAK2-STAT Pathway in the Growth Hormone Signal Transduction

Post-Receptor Inhibitors of the GHR-JAK2-STAT Pathway in the Growth Hormone Signal Transduction

Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice

Control of Liver Gene Expression by Sex Steroids and Growth Hormone Interplay

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