Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism.

Edery, Marc; Rozakis-Adcock, Maria; Goujon, Laure; Finidori, J.; Lévi-Meyrueis, Corinne; Paly, J.; Djiane, Jean; Postel-Vinay, Marie-Catherine; Kelly, Paul A.

doi:10.1172/jci116304

Cited by 31 publications

(6 citation statements)

References 29 publications

(25 reference statements)

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“…These BPs bind hGH with very low affinity (10 6 -10 5 M Ϫ1 ) and high capacity (between 2 and 15 µg/ml) and are thought not to be related to the GH receptor (Baumann and Shaw, 1990;Tar et al, 1990). However, there are high molecular weight complexes in murine serum (Smith and Talamantes, 1987) and also in the culture medium of cells transfected with rabbit GH-BP cDNA (Edery et al, 1993). These data suggest that circulating multimers of GH-BP may arise after proteolysis of the membrane bound GH receptor.…”

Section: Discussionmentioning

confidence: 99%

Identification and Modulation of a Growth Hormone-Binding Protein in Rainbow Trout (Oncorhynchus mykiss) Plasma during Seawater Adaptation

Sohm

Manfroid

Pezet

et al. 1998

General and Comparative Endocrinology

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A soluble protein that specifically bound 125 I-human growth hormone (hGH) was identified in rainbow trout plasma, using HPLC-gel filtration. The binding affinity of the protein for hGH was 1.2 ؋ 10 9 M ؊1 . 125 I-rainbow trout GH (tGH) was also able to bind to the protein albeit with a lower affinity (6.6 ؋ 10 7 M ؊1 ) than hGH. Crosslinking experiments using 125 I-hGH revealed two specific bands of 150 and 130 kDa. The complex 125 I-hGH-BP could be precipitated by a monoclonal anti-GH receptor antibody, suggesting a close relationship between the plasma GH-BP and the GH receptor. A fourfold increase in the hGH binding to the GH-BP was shown 48 h after transfer of the fishes from freshwater to seawater. The increase in binding was related to a high binding capacity without significant changes in binding affinity. These results suggest a potential role of this related GH-BP as an index of GH effects during seawater adaptation in salmonids.1998 Academic Press

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Section: Discussionmentioning

confidence: 99%

Identification and Modulation of a Growth Hormone-Binding Protein in Rainbow Trout (Oncorhynchus mykiss) Plasma during Seawater Adaptation

Sohm

Manfroid

Pezet

et al. 1998

General and Comparative Endocrinology

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“…To date, molecular biology provides the means to detect GHR mutations (4-6). In addition, it must be shown by transfection experiments that a mutation is functionally relevant (22). This, of course, would be the ideal approach the gold standardto classify clearly a patient as having primary GHIS.…”

Section: Discussionmentioning

confidence: 99%

Improvement of diagnostic criteria in growth hormone insensitivity syndrome: solutions and pitfalls

et al. 1994

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A survey to identify children and adolescents with primary growth hormone insensitivity syndrome (GHIS) yielded 38 patients who were positively identified using a scoring system that included five criteria: height, basal growth hormone (GH), GH binding protein, basal insulin‐like growth factor 1 (1GF‐I) and the increase of IGF‐I after 4 days of GH administration (IGF generation test). Because of an overlap of the accepted and excluded groups with respect to points scored, an attempt was made to improve the scoring system. The new criteria were: height below –3 SDS, basal GH 4 mU/I or above, GH binding below 10%, basal IGF‐I and basal IGF binding protein‐3 (IGFBP‐3) below the 0.1 centile for age, an increase of IGF‐I in the IGF generation test less than 15 μg/1, and the increase of IGFBP‐3 less than 0.4 mg/1. With this scoring system, a clear separation between the accepted and the excluded groups was obtained. IGFBP‐3 was included to give the GH‐dependent parameters of the IGF system more weight and because the accuracy of IGFBP‐3 in the IGF generation tests was greater than the accuracy of IGF‐I, when the group of patients with GHIS was compared with a group of patients with GH deficiency. Unexpectedly, the IGF generation test was unable to segregate both cohorts completely. In the GHIS‐positive group, a significant correlation was found between basal IGF‐I or IGFBP‐3 levels corrected for age (SDS) and height SDS (r= 0.49, p < 0.002 and r= 0.61, p < 0.0001, respectively). There was also a significant correlation between the changes of IGF‐I or IGFBP‐3 in the IGF generation test and height SDS. That is, the patients with a slight response to GH were those with the least growth retardation, suggesting the existence of partial GH insensitivity.

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“…Forty-eight hours after transfection, the cells were washed twice with PBS, fixed with 3% paraformaldehyde, and permeabilized with Triton as described previously (37) or were left nonpermeabilized. Forty-eight hours after transfection, the cells were washed twice with PBS, fixed with 3% paraformaldehyde, and permeabilized with Triton as described previously (37) or were left nonpermeabilized.…”

Section: Immunofluorescence Assaysmentioning

confidence: 99%

Four Contiguous Amino Acid Substitutions, Identified in Patients with Laron Syndrome, Differently Affect the Binding Affinity and Intracellular Trafficking of the Growth Hormone Receptor¹

Wojcik

Berg

Esposito

et al. 1998

The Journal of Clinical Endocrinology & Metabolism

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We have analyzed the GH receptor (GHR) gene in four individuals with Laron syndrome, and a missense mutation was identified for each patient in the extracellular domain of the GHR (D152H, I153T, Q154P, and V155G). The D152H mutation was previously reported. We have reproduced the three novel mutations in the GHR complementary DNA and analyzed their consequences in human 293 transfected cells. In cells expressing the I153T and V155G mutants, binding of [125I]human GH at the cell surface was very low, whereas binding to total membrane fractions was much less affected, suggesting impaired cell surface expression. Binding assays with cells expressing the Q154P mutant revealed severe defects both at the cell surface and in total particulate membrane fractions. Immunofluorescence experiments confirmed that cell surface expression of the three mutants was altered, and colocalization studies suggested that most of the mutant receptors are retained in the endoplasmic reticulum. Endoglycosidase H resistance tests also indicated that the majority of I153T and V155G GHRs are trapped in the endoplasmic reticulum. Thus, mutations on contiguous amino acids of the GHR result in various defects. The I153T, Q154P, and V155G mutations mainly affect intracellular trafficking and binding affinity of the receptor, whereas the D152H mutation affects receptor expression, dimerization, and signaling.

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Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism.

Cited by 31 publications

References 29 publications

Identification and Modulation of a Growth Hormone-Binding Protein in Rainbow Trout (Oncorhynchus mykiss) Plasma during Seawater Adaptation

Identification and Modulation of a Growth Hormone-Binding Protein in Rainbow Trout (Oncorhynchus mykiss) Plasma during Seawater Adaptation

Improvement of diagnostic criteria in growth hormone insensitivity syndrome: solutions and pitfalls

Four Contiguous Amino Acid Substitutions, Identified in Patients with Laron Syndrome, Differently Affect the Binding Affinity and Intracellular Trafficking of the Growth Hormone Receptor¹

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Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism.

Cited by 31 publications

References 29 publications

Identification and Modulation of a Growth Hormone-Binding Protein in Rainbow Trout (Oncorhynchus mykiss) Plasma during Seawater Adaptation

Identification and Modulation of a Growth Hormone-Binding Protein in Rainbow Trout (Oncorhynchus mykiss) Plasma during Seawater Adaptation

Improvement of diagnostic criteria in growth hormone insensitivity syndrome: solutions and pitfalls

Four Contiguous Amino Acid Substitutions, Identified in Patients with Laron Syndrome, Differently Affect the Binding Affinity and Intracellular Trafficking of the Growth Hormone Receptor1

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Four Contiguous Amino Acid Substitutions, Identified in Patients with Laron Syndrome, Differently Affect the Binding Affinity and Intracellular Trafficking of the Growth Hormone Receptor¹