Growth‐hormone‐receptor and cytokine‐receptor‐family signaling

Moutoussamy, Soraya; Kelly, Paul A.; Finidori, J.

doi:10.1046/j.1432-1327.1998.2550001.x

Cited by 110 publications

(83 citation statements)

References 24 publications

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“…Briefly, cells were transfected with a Stat5-responsive luciferase reporter gene construct (41,42) and treated with increasing amounts of GH (wt-GH and GH-P59S) for 6 h. Luciferase expression was then measured by the dual-luciferase reporter assay (Promega) on a luminometer (Mediators PhL, Aureon Biosystems, Vienna, Austria).…”

Section: Luciferase Reporter Gene Assay Of Stat5 Activationmentioning

confidence: 99%

Short stature in two siblings heterozygous for a novel bioinactive GH mutant (GH-P59S) suggesting that the mutant also affects secretion of the wild-type GH

Petkovic

Miletta

Boot

et al. 2013

European Journal of Endocrinology

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Objective: Short stature caused by biologically inactive GH is clinically characterized by lack of GH action despite normal-high secretion of GH, pathologically low IGF1 concentrations and marked catch-up growth on GH replacement therapy. Design and methods: Adopted siblings (girl and a boy) of unknown family history were referred for assessment of short stature (K4.5 and K5.6 SDS) at the age of 10 and 8.1 years respectively. They had delayed bone ages (6.8 and 4.5 years), normal GH peaks at stimulation tests, and severely reduced IGF1 concentrations (K3.5 and K4.0 SDS). Genetic analysis of the GH1 gene showed a heterozygous P59S mutation at position involved in binding to GH receptor (GHR). Results: Isoelectric focusing analysis of secreted GH in patient serum revealed the presence of higher GH-P59S peak compared with that of wt-GH. Furthermore, computational simulation of GH-P59S binding to GHR suggested problems in correct binding of the mutant to the GHR. In vitro GHR binding studies revealed reduced binding affinity of GH-P59S for GHR (IC 50 , 30 ng/ml) when compared with the wt-GH (IC 50 , 11.8 ng/ml) while a significantly decreased ability of the mutant to activate the Jak2/Stat5 signaling pathway was observed at physiological concentrations of 25-100 ng/ml. Conclusions: The clinical and biochemical data of our patients support the diagnosis of partial bioinactive GH syndrome. The higher amount of GH-P59S secreted in their circulation combined with its impact on the wt-GH function on GHR binding and signaling may alter GHR responsiveness to wt-GH and could ultimately explain severe short stature found in our patients.

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Section: Luciferase Reporter Gene Assay Of Stat5 Activationmentioning

confidence: 99%

Short stature in two siblings heterozygous for a novel bioinactive GH mutant (GH-P59S) suggesting that the mutant also affects secretion of the wild-type GH

Petkovic

Miletta

Boot

et al. 2013

European Journal of Endocrinology

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“…Insulin, IGF-1, epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) bind to transmembrane receptors containing tyrosine kinase domains whereas GH and cytokine receptors do not possess tyrosine kinase activity but mediate their effect through cytoplasmic kinase proteins. On the other hand, transforming growth factor (TGF)-β stimulates a receptor containing serine/threonine kinase activity, whereas catecholamines, prostaglandins, adenosine and angiotensin-II bind G protein-associated receptors [35,52,58,100,157,160,164,197,217].…”

Section: Extracellular Agents Acting Through Transmembrane Receptorsmentioning

confidence: 99%

“…The hormonal agents acting through transmembrane receptors activate numerous intracellular pathways that are progressively better understood [35,100,157,160,164,197]. Specific regulation of these downstream events could explain some of the divergent adipogenic and/or antiadipogenic effects observed with hormonal factors according to the origin of the preadipocytes.…”

Section: Regulation Of Adipose Conversion By Second Messengersmentioning

confidence: 99%

The adipose conversion process: regulation by extracellular and intracellular factors

Boone

Mourot

Gregoire³

et al. 2000

Reprod. Nutr. Dev.

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-White adipose tissue regulates lipid metabolism and acts as a secretory organ. Because of its importance for human health and animal production, many studies have attempted to better understand its development at the cellular and molecular levels by culturing preadipose cells in vitro. This synthesis article describes our current knowledge, acquired by this approach, concerning the regulation of the different steps of the adipocyte differentiation program by extracellular (hormones, cytokines, growth factors, retinoids and fatty acids) and intracellular agents (second messengers and transcription factors). The discrepant effects that have been observed for some of these factors are also discussed. This information is very important in the perspective of a better control of fat deposits in human and breeding species.preadipocyte / differentiation / hormonal agent / second messenger / transcription factor Résumé -Le processus d'adipoconversion : sa régulation par des facteurs extracellulaires et intracellulaires. Le tissu adipeux blanc régule le métabolisme lipidique et agit comme un organe de sécrétion. Étant donné son importance pour la santé humaine et la production animale, de nombreuses études ont tenté de mieux comprendre son développement aux niveaux cellulaire et moléculaire en utilisant des cultures de préadipocytes. Cet article de synthèse décrit notre connaissance actuelle, issue de cette approche, concernant la régulation des différentes étapes du programme de la diffé-renciation adipocytaire par des facteurs extracellulaires (hormones, cytokines, facteurs de croissance, rétinoïdes et acides gras) et intracellulaires (seconds messagers et facteurs de transcription). Les effets divergents observés pour certains de ces facteurs sont également discutés. Ces informations sont très importantes dans la perspective d'un meilleur contrôle des dépôts adipeux chez l'humain et les espèces d'élevage.préadipocyte / différenciation / hormone / second messager / facteur de transcription Reprod. Nutr. Dev. 40 (2000) 325-358 325

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“…Instead, they depend upon receptorassociated Janus kinase tyrosine kinases to initiate signaling after ligand binding (5)(6)(7). These Janus kinases become activated and phosphorylate themselves, the cytokine receptor to which they are bound, and Src homology domain 2-containing signaling/adapter proteins, including Stat transcription factors (6,7). This family of transcription factors includes Stats1, -2, -3, -4, -5a, -5b, and -6, where Stat5a and Stat5b are two separate but homologous gene products (95% amino acid identity) (8).…”

mentioning

confidence: 99%

Insulin Induction of SOCS-2 and SOCS-3 mRNA Expression in C2C12 Skeletal Muscle Cells Is Mediated by Stat5*

Sadowski¹,

Choi

Le³

et al. 2001

Journal of Biological Chemistry

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Previously, by a yeast 2-hybrid screen, we identified signal transducer and activator of transcription 5b (Stat5b) as a substrate of the insulin receptor (IR). We demonstrated that refeeding of fasted mice leads to rapid activation of Stat5 proteins in liver, skeletal muscle, and fat, suggesting that Stat5b is a physiological target of insulin. Here, we show that injection of glucose or insulin into fasted mice leads to robust activation of both Stat5a and Stat5b in skeletal muscle. In C2C12 myotubes, we find that insulin stimulates tyrosine phosphorylation of Stat5a and Stat5b by 3-5-fold. This degree of Stat5 activation in vitro is significantly lower than what we observe in vivo and inversely correlates with IRS-1/2 levels. We can recapitulate robust insulin activation of Stat5 in C2C12 cells by stable overexpression of the human IR (hIR). To identify insulin-activated genes that are Stat5 targets, we also overexpressed an IR mutant (LA-hIR) that signals normally for mitogenactivated protein kinase-and phosphatidylinositol 3-kinase-dependent pathways but is deficient in Stat5 signaling in response to insulin. We demonstrate that insulin induces the expression of SOCS-2 mRNA in the wild type hIR but not in the LA-hIR-overexpressing cells. The induction of SOCS-3 by insulin is reduced but not lost in the LA-hIR cells. Therefore, our results suggest that insulin induction of SOCS-2, and in part SOCS-3 mRNA expression, is mediated by Stat5 and can be independent of mitogen-activated protein kinase and phosphatidylinositol 3-kinase-signaling pathways.Insulin plays a pivotal role in the regulation of glucose homeostasis and exerts numerous metabolic and proliferative responses in insulin-sensitive tissues (1). These effects are mediated by the binding of insulin and subsequent activation of the insulin receptor (IR) 1 tyrosine kinase (1). The activated receptor phosphorylates itself as well as several other intracellular substrates. Unlike several members of the receptor tyrosine kinase superfamily, which directly recruit and phosphorylate signaling/adapter proteins, the IR mainly signals by recruiting and phosphorylating members of the insulin receptor substrate family, IRS-1, -2, -3, and -4, Gab1 and -2, and p62dok-1, -2, and -3 (2, 3). These proteins then serve as multivalent docking sites for the recruitment of other Src homology domain 2-containing signaling proteins. Subsequently, at least two major signal transduction cascades are initiated including the mitogen-activated protein kinase-and phosphatidylinositol 3Ј-kinase-signaling pathways, which propagate the signal to various cytoplasmic and nuclear effectors (1, 4).Unlike the IR, cytokine receptors do not possess intrinsic tyrosine kinase activity. Instead, they depend upon receptorassociated Janus kinase tyrosine kinases to initiate signaling after ligand binding (5-7). These Janus kinases become activated and phosphorylate themselves, the cytokine receptor to which they are bound, and Src homology domain 2-containing signaling/adapter proteins, includin...

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Growth‐hormone‐receptor and cytokine‐receptor‐family signaling

Cited by 110 publications

References 24 publications

Short stature in two siblings heterozygous for a novel bioinactive GH mutant (GH-P59S) suggesting that the mutant also affects secretion of the wild-type GH

Short stature in two siblings heterozygous for a novel bioinactive GH mutant (GH-P59S) suggesting that the mutant also affects secretion of the wild-type GH

The adipose conversion process: regulation by extracellular and intracellular factors

Insulin Induction of SOCS-2 and SOCS-3 mRNA Expression in C2C12 Skeletal Muscle Cells Is Mediated by Stat5*

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