The Growth Hormone Receptor (GHR) c.899dupC mutation functions as a dominant negative: Insights into the pathophysiology of intracellular GHR defects

Journal of Clinical Endocrinology and Metabolism

Volumn 96, Issue 11, 2011, Pages

  Derr, Michael A ^a   Aisenberg, Javier ^b   Fang, Peng ^a   Tenenbaum Rakover, Yardena ^c   Rosenfeld, Ron G ^a   Hwa, Vivian ^a  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b HACKENSACK UNIVERSITY MEDICAL CENTER   (United States)

^c HAEMEK MEDICAL CENTER   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH HORMONE RECEPTOR; STAT5B PROTEIN;

ADOLESCENT; ADULT; ARTICLE; CELL LEVEL; CHILD; CONTROLLED STUDY; DOMINANT NEGATIVE MUTATION; EMBRYO; FEMALE; GENE ACTIVITY; GENE FUNCTION; GENE INTERACTION; GENE MUTATION; GENETIC VARIABILITY; GROWTH HORMONE DEFICIENCY; HETEROZYGOSITY; HORMONE RESPONSE; HUMAN; HUMAN CELL; MALE; NONHUMAN; PATHOPHYSIOLOGY; PRESCHOOL CHILD; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SCHOOL CHILD; WILD TYPE;

HEK293 CELLS; HUMANS; INSULIN-LIKE GROWTH FACTOR I; LARON SYNDROME; MUTATION; PHOSPHORYLATION; RECEPTORS, SOMATOTROPIN; SIGNAL TRANSDUCTION; STAT5 TRANSCRIPTION FACTOR;

EID: 80655130414     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2011-1597     Document Type: Article

References (32)

1. Rosenfeld RG, Hwa V 2009 The growth hormone cascade and its role in mammalian growth. Horm Res 71:36-40
2. David A, Hwa V, Metherell LA, Netchine I, Camacho-Hübner C, Clark AJ, Rosenfeld RG, Savage MO 2011 Evidence for a continuum of genetic, phenotypic, and biochemical abnormalities in children with growth hormone insensitivity. Endocr Rev 32:472-497
3. Savage MO, Attie KM, David A, Metherell LA, Clark AJ, Camacho-Hübner C 2006 Endocrine assessment, molecular characterization and treatment of growth hormone insensitivity disorders. Nat Clin Pract Endocrinol Metab 2:395-407 (Pubitemid 44050109)
4. Rosenfeld RG, Belgorosky A, Camacho-Hubner C, Savage MO,Wit JM, Hwa V 2007 Defects in growth hormone receptor signaling. Trends Endocrinol Metab 18:134-141 (Pubitemid 46629026)
5. Hwa V, Nadeau K, Wit JM, Rosenfeld RG 2011 STAT5b deficiency: lessons from STAT5b gene mutations. Best Pract Res Clin Endocrinol Metab 25:61-75
6. Domené HM, Hwa V, Argente J, Wit JM, Wit JM, Camacho-Hübner C, Jasper HG, Pozo J, van Duyvenvoorde HA, Yakar S, Fofanova- Gambetti OV, Rosenfeld RG 2009 Human acid-labile subunit deficiency: clinical, endocrine and metabolic consequences. Horm Res 72:129-141
7. Woods KA, Camacho-Hübner C, Savage MO, Clark AJ 1996 Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med 335:1363-1367
8. de Vos AM, Ultsch M, Kossiakoff AA 1992 Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science 255:306-312
9. Behncken SN, Waters MJ 1999 Molecular recognition events involved in the activation of the growth hormone receptor by growth hormone. J Mol Recognit 12:355-362 (Pubitemid 30047295)
10. Derr MA, Fang P, Sinha SK, Ten S, Hwa V, Rosenfeld RG 2011 A novel Y332C missense mutation in the intracellular domain of the human growth hormone receptor does not alter STAT5b signaling: redundancy of GHR intracellular tyrosines involved in STAT5b signaling. Horm Res Paediatr 75:187-199
11. Aisenberg J, Auyeung V, Pedro HF, Sugalski R, Chartoff A, Rothenberg R, Derr MA, Hwa V, Rosenfeld RG 2010 Atypical GH insensitivity syndrome and severe insulin-like growth factor-I deficiency resulting from compound heterozygous mutations of the GHreceptor, including a novel frameshift mutation affecting the intracellular domain. Horm Res Paediatr 74:406-411
12. Goddard AD, Covello R, Luoh SM, Clackson T, Attie KM, Gesundheit N, Rundle AC, Wells JA, Carlsson LM 1995 Mutations of the growth hormone receptor in children with idiopathic short stature. The Growth Hormone Insensitivity Study Group. N Engl J Med 333:1093-1098
13. Ross RJ, Esposito N, Shen XY, Von Laue S, Chew SL, Dobson PR, Postel-Vinay MC, Finidori J 1997 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 11:265-273 (Pubitemid 27106322)
14. Fang P, Riedl S, Amselem S, Pratt KL, Little BM, Haeusler G, Hwa V, Frisch H, Rosenfeld RG 2007 Primary growth hormone (GH) insensitivity and IGF deficiency caused by novel compound heterozygous mutations of the GH receptor gene: genetics and functional studies of simple and compound heterozygous states. J Clin Endocrinol Metab 92:2223-2231 (Pubitemid 46997127)
15. Hwa V, Little B, Kofoed EM, Rosenfeld RG 2004 Transcriptional regulation of insulin-like growth factor-I (IGF-I) by interferon-γ(IFN-g) requires STAT-5b. J Biol Chem 279:2728-2736 (Pubitemid 38114262)
16. Harding PA, Wang XZ, Kelder B, Souza S, Okada S, Kopchick JJ 1994 In vitro mutagenesis of growth hormone receptor Asn-linked glycosylation sites. Mol Cell Endocrinol 106:171-180
17. van den Eijnden MJ, Lahaye LL, Strous GJ 2006 Disulfide bonds determine growth hormone receptor folding, dimerisation and ligand binding. J Cell Sci 119:3078-3086
18. Ayling RM, Ross R, Towner P, Von Laue S, Finidori J, Moutoussamy S, Buchanan CR, Clayton PE, Norman MR 1997 A dominant negative mutation of the growth hormone receptor causes familial short stature. Nat Genet 16:13-14
19. Iida K, Takahashi Y, Kaji H, Nose O, Okimura Y, Abe H, Chihara K 1998 Growth hormone (GH) insensitivity syndrome with high serum GH-binding protein levels caused by a heterozygous splice site mutation of the GH receptor gene producing a lack of intracellular domain. J Clin Endocrinol Metab 83:531-537 (Pubitemid 28496535)
20. Iida K, Takahashi Y, Kaji H, Takahashi MO, Okimura Y, Nose O, Abe H, Chihara K 1999 Functional characterization of truncated growth hormone (GH) receptor-(1-277) causing partial GH insensitivity syndrome with high GH-binding protein. J Clin Endocrinol Metab 84:1011-1016 (Pubitemid 29138235)
21. Metherell LA, Akker SA, Munroe PB, Rose SJ, Caulfield M, Savage MO, Chew SL, Clark AJ 2001 Pseudoexon activation as a novel mechanism for disease resulting in atypical growth-hormone insensitivity. Am J Hum Genet 69:641-646 (Pubitemid 32777702)
22. David A, Camacho-Hübner C, Bhangoo A, Rose SJ, Miraki-Moud F, Akker SA, Butler GE, Ten S, Clayton PE, Clark AJ, Savage MO, Metherell LA 2007 An intronic growth hormone receptor mutation causing activation of a pseudoexon is associated with a broad spectrum of growth hormone insensitivity phenotypes. J Clin Endocrinol Metab 92:655-659
23. Maamra M, Milward A, Esfahani HZ, Abbott LP, Metherell LA, Savage MO, Clark AJ, Ross RJ 2006 A 36 residues insertion in the dimerization domain of the growth hormone receptor results in defective trafficking rather than impaired signaling. J Endocrinol 188:251-261 (Pubitemid 43273813)
24. Gastier JM, Berg MA, Vesterhus P, Reiter EO, Francke U 2000 Diverse deletions in the growth hormone receptor gene cause growth hormone insensitivity syndrome. Hum Mutat 16:323-333
25. Kaji H, Nose O, Tajiri H, Takahashi Y, Iida K, Takahashi T, Okimura Y, Abe H, Chihara K 1997 Novel compound heterozygous mutations of growth hormone (GH) receptor gene in a patient with GHinsensitivity syndrome. J Clin Endocrinol Metab 82:3705-3709 (Pubitemid 27509359)
26. Milward A, Metherell L, Maamra M, Barahona MJ, Wilkinson IR, Camacho-Hübner C, Savage MO, Bidlingmaier M, Bidlingmaier CM, Clark AJ, Ross RJ, Webb SM 2004 Growth hormone (GH) insensitivity syndrome due to a GH receptor truncated after Box 1, resulting in isolated failure of STAT 5 signal transduction. J Clin Endocrinol Metab 89:1259-1266 (Pubitemid 38368423)
27. Tiulpakov A, Rubtsov P, Dedov I, Peterkova V, Bezlepkina O, Chrousos GP, Hochberg Z 2005 A novel C-terminal growth hormone receptor (GHR) mutation results in impaired GHR-STAT5 but normal STAT-3 signaling. J Clin Endocrinol Metab 90:542-547 (Pubitemid 40116706)
28. Brown RJ, Adams JJ, Pelekanos RA, Wan Y, McKinstry WJ, Palethorpe K, Seeber RM, Monks TA, Eidne KA, Parker MW, Waters MJ 2005 Model for growth hormone receptor activation based on subunit rotation within a receptor dimer. Nat Struct Mol Biol 12:814-821 (Pubitemid 43086257)
29. Kou K, Lajara R, Rotwein P 1993 Amino acid substitutions in the intracellular part of the growth hormone receptor in a patient with the Laron syndrome. J Clin Endocrinol Metab 76:54-59 (Pubitemid 23027552)
30. Goddard AD, Dowd P, Chernausek S, Geffner M, Gertner J, Hintz R, Hopwood N, Kaplan S, Plotnick L, Rogol A, Rosenfield R, Saenger P, Mauras N, Hershkopf R, Angulo M, Attie K 1997 Partial growth-hormone insensitivity: the role of growth-hormone receptor mutations in idiopathic short stature. J Pediatr 131:S51-S55 (Pubitemid 27505699)
31. Chujo S, Kaji H, Takahashi Y, Okimura Y, Abe H, Chihara K 1996 No correlation of growth hormone receptor gene mutation P561T with body height. Eur J Endocrinol 134:560-562 (Pubitemid 26189097)
32. Iida K, Takahashi Y, Kaji H, Onodera N, Takahashi MO, Okimura Y, Abe H, Chihara K 1999 The C422F mutation of the growth hormone receptor gene is not responsible for short stature. J Clin Endocrinol Metab 84:4214-4219 (Pubitemid 30644220)