| An activating mutation of AKT2 and human hypoglycemia. | |
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MedLine Citation:
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PMID: 21979934 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pathological fasting hypoglycemia in humans is usually explained by excessive circulating insulin or insulin-like molecules or by inborn errors of metabolism impairing liver glucose production. We studied three unrelated children with unexplained, recurrent, and severe fasting hypoglycemia and asymmetrical growth. All were found to carry the same de novo mutation, p.Glu17Lys, in the serine/threonine kinase AKT2, in two cases as heterozygotes and in one case in mosaic form. In heterologous cells, the mutant AKT2 was constitutively recruited to the plasma membrane, leading to insulin-independent activation of downstream signaling. Thus, systemic metabolic disease can result from constitutive, cell-autonomous activation of signaling pathways normally controlled by insulin. |
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Authors:
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K Hussain; B Challis; N Rocha; F Payne; M Minic; A Thompson; A Daly; C Scott; J Harris; B J L Smillie; D B Savage; U Ramaswami; P De Lonlay; S O'Rahilly; I Barroso; R K Semple |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-10-06 |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 334 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-28 Completed Date: 2011-11-02 Revised Date: 2012-05-01 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 474 Citation Subset: IM |
Affiliation:
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Clinical and Molecular Genetics Unit, Developmental Endocrinology Research Group, Institute of Child Health, University College London, London WC1N 1EH, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution Cell Membrane / metabolism Cell Nucleus / metabolism Child Female Growth HeLa Cells Heterozygote Humans Hypoglycemia / genetics*, metabolism* Insulin / blood, metabolism Male Mosaicism Mutation* Pedigree Protein Interaction Domains and Motifs Proto-Oncogene Proteins c-akt / chemistry, genetics*, metabolism Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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077016//Wellcome Trust; 077016/Z/05/Z//Wellcome Trust; 078986//Wellcome Trust; 078986/Z/06/Z//Wellcome Trust; 080952//Wellcome Trust; 080952/Z/06/Z//Wellcome Trust; 091551//Wellcome Trust; 091551/Z/10/Z//Wellcome Trust; //Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Insulin; EC 2.7.1.37/AKT2 protein, human; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
| Comments/Corrections | |
Comment In:
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Cell Metab. 2011 Dec 7;14(6):722-3
[PMID:
22152300
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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