[SOMA_HUMAN] Defects in GH1 are a cause of growth hormone deficiency isolated type 1A (IGHD1A) [MIM:262400]; also known as pituitary dwarfism I. IGHD1A is an autosomal recessive deficiency of GH which causes short stature. IGHD1A patients have an absence of GH with severe dwarfism and often develop anti-GH antibodies when given exogenous GH. Defects in GH1 are a cause of growth hormone deficiency isolated type 1B (IGHD1B) [MIM:612781]; also known as dwarfism of Sindh. IGHD1B is an autosomal recessive deficiency of GH which causes short stature. IGHD1B patients have low but detectable levels of GH. Dwarfism is less severe than in IGHD1A and patients usually respond well to exogenous GH. Defects in GH1 are the cause of Kowarski syndrome (KWKS) [MIM:262650]; also known as pituitary dwarfism VI. Defects in GH1 are a cause of growth hormone deficiency isolated type 2 (IGHD2) [MIM:173100]. IGHD2 is an autosomal dominant deficiency of GH which causes short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. [GHR_HUMAN] Defects in GHR are a cause of Laron syndrome (LARS) [MIM:262500]. A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone. Defects in GHR may be a cause of idiopathic short stature autosomal (ISSA) [MIM:604271]. Short stature is defined by a subnormal rate of growth.
[SOMA_HUMAN] Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues. [GHR_HUMAN] Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity). The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling. Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.
Remodeling of the interface between human growth hormone (hGH) and the extracellular domain of its receptor was studied by deleting a critical tryptophan residue (at position 104) in the receptor, creating a large cavity, and selecting a pentamutant of hGH by phage display that fills the cavity and largely restores binding affinity. A 2.1 A resolution x-ray structure of the mutant complex showed that the receptor cavity was filled by selected hydrophobic mutations of hGH. Large structural rearrangements occurred in the interface at sites that were distant from the mutations. Such plasticity may be a means for protein-protein interfaces to adapt to mutations as they coevolve.
Structural plasticity in a remodeled protein-protein interface.,Atwell S, Ultsch M, De Vos AM, Wells JA Science. 1997 Nov 7;278(5340):1125-8. PMID:9353194
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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↑ Walker JL, Crock PA, Behncken SN, Rowlinson SW, Nicholson LM, Boulton TJ, Waters MJ. A novel mutation affecting the interdomain link region of the growth hormone receptor in a Vietnamese girl, and response to long-term treatment with recombinant human insulin-like growth factor-I and luteinizing hormone-releasing hormone analogue. J Clin Endocrinol Metab. 1998 Jul;83(7):2554-61. PMID:9661642
↑ Wojcik J, Berg MA, Esposito N, Geffner ME, Sakati N, Reiter EO, Dower S, Francke U, Postel-Vinay MC, Finidori J. Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor. J Clin Endocrinol Metab. 1998 Dec;83(12):4481-9. PMID:9851797
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↑ Atwell S, Ultsch M, De Vos AM, Wells JA. Structural plasticity in a remodeled protein-protein interface. Science. 1997 Nov 7;278(5340):1125-8. PMID:9353194