Hormone Research in Paediatrics
Sensitivity to Growth Hormone
Growth Hormone Receptor Signalling and Actions in Bone GrowthKelly P.A. · Finidori J. · Moulin S. · Kedzia C. · Binart N.INSERM Unité 344 – Endocrinologie Moléculaire, Faculty of Médicine Necker, Paris, France
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Horm Res 2001;55(suppl 2):14–17
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Article / Publication Details
First-Page Preview
Published online: November 17, 2004
Issue release date: 2001
Number of Print Pages: 4
Number of Figures: 2
Number of Tables: 0
ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)
For additional information: https://www.karger.com/HRP
Abstract
Growth hormone (GH) acts by binding to a membrane receptor that is part of the cytokine receptor superfamily. Ligand binding induces receptor dimerization leading to activation of the associated tyrosine kinase, Janus kinase (Jak) 2. Transphosphorylation of Jak2 occurs followed by tyrosine phosphorylation of the receptor, and numerous cytoplasmic proteins. Among these are the signal transducers and activators of transcription (Stat) proteins, as well as adaptor proteins leading to the activation of the Ras/mitogen-activated protein (MAP) kinase and the phosphatidyl-inositol-3′-kinase (PI 3-kinase) pathways. Activation of the GH receptor system is relatively transient, with several mechanisms being involved in down-regulation: internalization and degradation of the receptor and recruitment of phosphatases or specific inhibitors of the Jak–Stat pathway, the suppressors of cytokine signalling (SOCS) proteins. Finally, the use of the GH receptor knock-out mouse model has allowed us to dissect the role of this hormone in post-natal body growth and homeostasis.
© 2001 S. Karger AG, Basel
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References
-
Leung DW, Spencer SA, Cachianes G, Hammonds RG, Collins C, Henzel WJ, Barnard R, Waters MJ, Wood WI: Growth hormone receptor and serum binding protein: purification, cloning, and expression. Nature 1987;330:537–543.
-
Boutin JM, Jolicoeur C, Okamura H, Gagnon J, Edery M, Shirota M, Banville D, Dusanter-Fourt I, Djiane J, Kelly PA: Cloning and expression of the rat prolactin receptor, a member of the growth hormone/prolactin receptor gene family. Cell 1988;53:69–77.
-
Finidori J: Regulators of growth hormone signaling. Vitam Horm 2000;59:71–97.
-
Murakami M, Narazaki M, Hibi M, Yawata H, Yasukawa K, Hamaguchi M, Taga T, Kishimoto T: Critical cytoplasmic region of the interleukin-6 signal transducer, gp130 is conserved in the cytokine receptor family. Proc Natl Acad Sci USA 1991;88:11349–11353.
-
Ross RJM, Esposito N, Shen XY, von Laue S, Chew SL, Dobson PRM, Postel-Vinay MC, Finidori J: A short isoform of the human growth hormone receptor functions as a dominant negative inhibitor of the full-length receptor and generates large amounts of binding protein. Mol Endocrinol 1997;11:265–273.
-
Baumbach WR, Horner DL, Logan JS: The growth hormone-binding protein in rat serum is an alternatively spliced form of the rat growth hormone receptor. Genes Dev 1989;3:1199–1205.
-
Smith WC, Kuniyoshi J, Talamantes F: Mouse serum growth hormone (GH) binding protein has GH receptor extracellular and substituted transmembrane domains. Mol Endocrinol 1989;3:984–990.
-
Sotiropoulos A, Goujon L, Simonin G, Kelly PA, Postel-Vinay MC, Finidori J: Evidence for generation of the growth hormone-binding protein through proteolysis of the growth hormone membrane receptor. Endocrinology 1993;132:1863–1865.
-
Alele J, Jiang J, Goldsmith JF, Yang X, Maheshwari HG, Black RA, Baumann G, Frank SJ: Blockade of growth hormone receptor shedding by a metalloprotease inhibitor. Endocrinology 1998;139:1927–1935.
-
De Vos AM, Ultsch M, Kossiakoff AA: Human growth hormone and extracellular domain of its receptor: Crystal structure of the complex. Science 1992;255:306–312.
-
Argetsinger LS, Campbell GS, Yang X, Witthuhn BA, Silvennoinen O, Ihle JN, Carter-Su C: Identification of Jak2 as a growth hormone receptor-associated tyrosine kinase. Cell 1993;74:237–244.
-
Frank SJ, Yi W, Zhao Y, Goldsmith JF, Gilliland G, Jiang J, Sakai I, Kraft AS: Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor. J Biol Chem 1995;270:14776–14785.
-
Sotiropoulos A, Perrot-Applanat M, Dinerstein H, Pallier A, Postel-Vinay MC, Finidori J, Kelly PA: Distinct cytoplasmic regions of the growth hormone receptor are required for activation of Jak2 mitogen-activated protein kinase, and transcription. Endocrinology 1994;135:1292–1298.
-
Girault JA, Labesse G, Mornon JP, Callebaut I: Janus kinases and focal adhesion kinases play in the 4.1 band: A superfamily of band 4.1 domains important for cell structure and signal transduction. Mol Med 1998;4:751–769.
-
Ram PA, Park S, Choi HK, Waxman DJ: Growth hormone activation of Stat1, Stat3 and Stat5 in rat liver. J Biol Chem 1996;271:5929–5940.
-
Sotiropoulos A, Moutoussamy S, Binart N, Kelly PA, Finidori J: The membrane proximal region of the cytoplasmic domain of the growth hormone receptor is involved in the activation of Stat 3. FEBS Lett 1995;369:169–172.
-
Smit LS, Meyer DJ, Billestrup N, Norstedt G, Schwartz J, Carter-Su C: The role of the growth hormone (GH) receptor and Jak1 and Jak2 kinases in the activation of Stats, 1, 3 and 5 by GH. Mol Endocrinol 1996;10:519–533.
-
Sotiropoulos A, Moutoussamy S, Renaudie F, Clauss M, Kayser C, Gouilleux F, Kelly PA, Finidori J: Differential activation of Stat3 and Stat5 by distinct regions of the growth hormone receptor. Mol Endocrinol 1996;10:998–1009.
-
Zhou YC, Waxman DJ: Cross-talk between janus kinase-signal transducer and activator of transcription (JAK–STAT) and peroxisome proliferator-activated receptor-α (PPARα) signaling pathways. Growth hormone inhibition of pparα transcriptional activity mediated by Stat5b. J Biol Chem 1999;274:2672–2681.
-
Vanderkuur JA, Butch ER, Waters SB, Pessin JE, Guan KL, Carter-Su C: Signaling molecules involved in coupling growth hormone receptor to mitogen-activated protein kinase activation. Endocrinology 1997;138:4301–4307.
-
Yamauchi T, Ueki K, Tobe K, Tamemoto H, Sekine N, Wada M, Honjo M, Takahashi M, Takahashi T, Hirai H, Tushima T, Akanuma Y, Fujita T, Komuro I, Yazaki Y, Kadowaki T: Tyrosine phosphorylation of the EGF receptor by the kinase Jak2 is induced by growth hormone. Nature 1997;390:91–96.
-
Argetsinger LS, Hsu GW, Myers MGJ, Billestrup N, White M, Carter-Su C: Growth hormone, interferon-γ, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1. J Biol Chem 1995;270:14685–14692.
-
Moutoussamy S, Renaudie F, Lago F, Kelly PA, Finidori J: Grb10 identified as a potential regulator of growth hormone (GH) signaling by cloning of GH receptor target proteins. J Biol Chem 1998;273:15906–15912.
-
Clarkson RE, Chen CM, Harrison S, Wells C, Muscat GO, Waters MJ: Early responses of transactivating factors to growth hormone in preadipocytes: differential regulation of CCAAT enhancer-binding protein-B (C/EBPβ and C/EBPγ). Mol Endocrinol 1995;9:108–120.
-
Sims NA, Clement-Lacroix P, da Ponte F, Bouali Y, Binart N, Moriggl R, Goffin V, Coschigano K, Gaillard-Kelly M, Kopchick J, Baron R, Kelly PA: Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat 5. J Clin Invest 2000;106:1095–1103.
Article / Publication Details
First-Page Preview
Published online: November 17, 2004
Issue release date: 2001
Number of Print Pages: 4
Number of Figures: 2
Number of Tables: 0
ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)
For additional information: https://www.karger.com/HRP
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