Identification of the First Patient with a Confirmed Mutation of the JAK-STAT System

Overview

Journal Pediatr Nephrol

Specialties Nephrology
Pediatrics

Date 2005 Feb 3

PMID 15688233

Citations 4

Authors

Ron G Rosenfeld

Eric Kofoed

Caroline Buckway

Brian Little

Katie A Woods

Junko Tsubaki

Katherine A Pratt

Liliana Bezrodnik

Hector Jasper

Alejandro Tepper

Juan J Heinrich

Vivian Hwa

Affiliations

Soon will be listed here.

Abstract

Growth hormone insensitivity (GHI) has been attributable, classically, to mutations in the gene for the GH receptor. After binding to the GH receptor, GH initiates signal transduction through a number of pathways, including the JAK-STAT pathway. We describe the first patient reported with a mutation in the gene for STAT5b, a protein critical for the transcriptional regulation of insulin-like growth factor-I.

Citing Articles

Growth Hormone Receptor Regulation in Cancer and Chronic Diseases.

Strous G, Almeida A, Putters J, Schantl J, Sedek M, Slotman J Front Endocrinol (Lausanne). 2020; 11:597573.

PMID: 33312162 PMC: 7708378. DOI: 10.3389/fendo.2020.597573.

"Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway.

Bousoik E, Montazeri Aliabadi H Front Oncol. 2018; 8:287.

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JAK2, but not Src family kinases, is required for STAT, ERK, and Akt signaling in response to growth hormone in preadipocytes and hepatoma cells.

Jin H, Lanning N, Carter-Su C Mol Endocrinol. 2008; 22(8):1825-41.

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Recent advances in growth hormone signaling.

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References

Godowski P, Leung D, Meacham L, Galgani J, Hellmiss R, KERET R . Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism. Proc Natl Acad Sci U S A. 1989; 86(20):8083-7. PMC: 298219. DOI: 10.1073/pnas.86.20.8083. View

Rosenfeld R, Hwa V . Toward a molecular basis for idiopathic short stature. J Clin Endocrinol Metab. 2004; 89(3):1066-7. DOI: 10.1210/jc.2004-0092. View

Freeth J, Silva C, Whatmore A, Clayton P . Activation of the signal transducers and activators of transcription signaling pathway by growth hormone (GH) in skin fibroblasts from normal and GH binding protein-positive Laron Syndrome children. Endocrinology. 1998; 139(1):20-8. DOI: 10.1210/endo.139.1.5690. View

Rosenfeld R, Rosenbloom A, Guevara-Aguirre J . Growth hormone (GH) insensitivity due to primary GH receptor deficiency. Endocr Rev. 1994; 15(3):369-90. DOI: 10.1210/edrv-15-3-369. View

Woods K, Fraser N, Postel-Vinay M, Savage M, Clark A . A homozygous splice site mutation affecting the intracellular domain of the growth hormone (GH) receptor resulting in Laron syndrome with elevated GH-binding protein. J Clin Endocrinol Metab. 1996; 81(5):1686-90. DOI: 10.1210/jcem.81.5.8626815. View

Teglund S, Mckay C, Schuetz E, Van Deursen J, Stravopodis D, Wang D . Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998; 93(5):841-50. DOI: 10.1016/s0092-8674(00)81444-0. View

Udy G, Towers R, Snell R, Wilkins R, Park S, Ram P . Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci U S A. 1997; 94(14):7239-44. PMC: 23803. DOI: 10.1073/pnas.94.14.7239. View

Rosenfeld R . Insulin-like growth factors and the basis of growth. N Engl J Med. 2003; 349(23):2184-6. DOI: 10.1056/NEJMp038156. View

Laron Z, Pertzelan A, Mannheimer S . Genetic pituitary dwarfism with high serum concentation of growth hormone--a new inborn error of metabolism?. Isr J Med Sci. 1966; 2(2):152-5. View

10.

Salerno M, Balestrieri B, Matrecano E, Officioso A, Rosenfeld R, Di Maio S . Abnormal GH receptor signaling in children with idiopathic short stature. J Clin Endocrinol Metab. 2001; 86(8):3882-8. DOI: 10.1210/jcem.86.8.7759. View

11.

Duquesnoy P, Sobrier M, Duriez B, Dastot F, Buchanan C, Savage M . A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization. EMBO J. 1994; 13(6):1386-95. PMC: 394956. DOI: 10.1002/j.1460-2075.1994.tb06392.x. View

12.

Ambrosio R, Fimiani G, Monfregola J, Sanzari E, De Felice N, Salerno M . The structure of human STAT5A and B genes reveals two regions of nearly identical sequence and an alternative tissue specific STAT5B promoter. Gene. 2002; 285(1-2):311-8. DOI: 10.1016/s0378-1119(02)00421-3. View

13.

Hwa V, Little B, Kofoed E, Rosenfeld R . Transcriptional regulation of insulin-like growth factor-I by interferon-gamma requires STAT-5b. J Biol Chem. 2003; 279(4):2728-36. DOI: 10.1074/jbc.M310495200. View

14.

Kofoed E, Hwa V, Little B, Woods K, Buckway C, Tsubaki J . Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med. 2003; 349(12):1139-47. DOI: 10.1056/NEJMoa022926. View