Osmoregulation in clinical disorders of thirst appreciation

McKenna, Kenneth Z.; Thompson, Christopher J.

doi:10.1046/j.1365-2265.1998.00572.x

Cited by 101 publications

(45 citation statements)

References 71 publications

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“…The crystal structure of Gα S revealed acidic residues in switch III that interact with basic ones in switch II and suggested that coupled dynamical changes in these two loop regions might be important for G-protein activation. Indeed, mutation of a conserved glutamate residue in switch III impairs receptor-mediated Gα S activation and the same residue is mutated in a patient with pseudohypoparathyroidism 30 . Mutation of the corresponding E232 residue in transducin decreases its downstream function, i.e.…”

Section: Discussionmentioning

confidence: 99%

A switch III motif relays signaling between a B12 enzyme and its G-protein chaperone

et al. 2013

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Fidelity during cofactor assembly is essential for the proper functioning of metalloenzymes and is ensured by specific chaperones. MeaB, a G-protein chaperone for the coenzyme B12-dependent radical enzyme, methylmalonyl-CoA mutase (MCM), utilizes the energy of GTP binding and/or hydrolysis to regulate cofactor loading into MCM, protect MCM from inactivation, and rescue MCM inactivated during turnover. Typically, G-proteins signal to client proteins using the conformationally mobile switch I and II loops. Crystallographic snapshots of MeaB reported herein reveal a novel switch III element, which exhibits substantial conformational plasticity. Using alanine-scanning mutagenesis, we demonstrate that the switch III motif is critical for bidirectional signal transmission of the GTPase activating protein activity of MCM and the chaperone functions of MeaB in the MeaB:MCM complex. Mutations in the switch III loop identified in patients corrupt this inter-protein communication and lead to methylmalonic aciduria, an inborn error of metabolism.

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Section: Discussionmentioning

confidence: 99%

A switch III motif relays signaling between a B12 enzyme and its G-protein chaperone

et al. 2013

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“…But only the deletion in exon 7 can be considered a hot spot mutation [8][9][10] involving about 35% of all mutations described. Shapira et al [11] reported two patients with Albright's hereditary osteodystrophy, multiple hormone resistance, and deficient Gsa activity.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel GNAS mutation for pseudohypoparathyroidism in a Chinese family

Sun

Cui

Zhao

et al. 2009

Endocr

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Pseudohypoparathyroidism (PHP) is a heterogeneous group of diseases characterized by hormone resistance to receptors that stimulate adenylate cyclase. PHP-Ia patients show specific Gs-alpha protein deficiency, PTH/TSH/gonadotropin resistance, and a phenotype characterized by Albright hereditary osteodystrophy (AHO). Many heterozygous mutations in the GNAS gene encoding the Gs protein have been identified in PHP-Ia. We describe two boys with hypocalcemia and elevated serum levels of PTH in a Chinese family. The 13 exons of the GNAS gene were amplified using 15 pairs of GNAS-specific primers and analyzed by direct sequencing. We found a novel frame shift mutation in exon 11 of the GNAS gene identified in both of the two boys and their mother. This report provides another example of a Gs-alpha mutation leading to PHP.

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“…Heterozygous inactivating mutations of the GNAS1 gene, encoding for the G Sα protein, have been associated with parathyroid and thyroid hormone resistance in AHO patients [5, 12, 13]. In a series of 8 patients with AHO and PHP IA, GNAS1 mutations were found in half of the cases [14]. …”

Section: Discussionmentioning

confidence: 99%

Albright’s Hereditary Osteodystrophy Associated with Cerebellar Pilocytic Astrocytoma: Coincidence or Genetic Relationship?

Sobottka¹,

Huebner

Haase³

et al. 2001

Horm Res Paediatr

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Albright’s hereditary osteodystrophy (AHO) is a rare inherited disease characterized by skeletal abnormalities, short stature, and, in some cases, resistance to parathyroid hormone, resulting in pseudohypoparathyroidism (PHP). Heterozygous inactivating mutations of the GNAS1 gene are responsible for reduced activity of the alpha subunit of the Gs protein (G_Sα), a protein that mediates hormone signal transduction across cell membranes. G_sα is also known to have oncogenic potentials, leading to the development of human pituitary tumors and Leydig cell tumors. Here, we report the 1st case, a 3.5-year-old girl, with classic AHO phenotype and PHP type 1A associated with a cerebellar pilocytic astrocytoma. Coincidence or genetic relationships of both diseases are discussed according to molecular findings and current literature.

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Osmoregulation in clinical disorders of thirst appreciation

Cited by 101 publications

References 71 publications

A switch III motif relays signaling between a B12 enzyme and its G-protein chaperone

A switch III motif relays signaling between a B12 enzyme and its G-protein chaperone

Identification of a novel GNAS mutation for pseudohypoparathyroidism in a Chinese family

Albright’s Hereditary Osteodystrophy Associated with Cerebellar Pilocytic Astrocytoma: Coincidence or Genetic Relationship?

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