Document Detail

Human SH2B1 mutations are associated with maladaptive behaviors and obesity.
MedLine Citation:
PMID:  23160192     Owner:  NLM     Status:  MEDLINE    
Src homology 2 B adapter protein 1 (SH2B1) modulates signaling by a variety of ligands that bind to receptor tyrosine kinases or JAK-associated cytokine receptors, including leptin, insulin, growth hormone (GH), and nerve growth factor (NGF). Targeted deletion of Sh2b1 in mice results in increased food intake, obesity, and insulin resistance, with an intermediate phenotype seen in heterozygous null mice on a high-fat diet. We identified SH2B1 loss-of-function mutations in a large cohort of patients with severe early-onset obesity. Mutation carriers exhibited hyperphagia, childhood-onset obesity, disproportionate insulin resistance, and reduced final height as adults. Unexpectedly, mutation carriers exhibited a spectrum of behavioral abnormalities that were not reported in controls, including social isolation and aggression. We conclude that SH2B1 plays a critical role in the control of human food intake and body weight and is implicated in maladaptive human behavior.
Michael E Doche; Elena G Bochukova; Hsiao-Wen Su; Laura R Pearce; Julia M Keogh; Elana Henning; Joel M Cline; Sadia Saeed; Anne Dale; Tim Cheetham; Inês Barroso; Lawrence S Argetsinger; Stephen O'Rahilly; Liangyou Rui; Christin Carter-Su; I Sadaf Farooqi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-19
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-03     Completed Date:  2013-02-04     Revised Date:  2014-07-16    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4732-6     Citation Subset:  AIM; IM    
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MeSH Terms
Adaptor Proteins, Signal Transducing / genetics*
Base Sequence
Case-Control Studies
Cell Movement
Child, Preschool
DNA Mutational Analysis
Energy Intake / genetics
Frameshift Mutation*
Genetic Association Studies
HEK293 Cells
Middle Aged
Mutation, Missense*
Obesity / genetics*
Protein Transport
Social Isolation
Young Adult
Grant Support
077016/Z/05/Z//Wellcome Trust; 082390/Z/07/Z//Wellcome Trust; 098497//Wellcome Trust; G0900554//Medical Research Council; G9824984//Medical Research Council; P30-CA46592/CA/NCI NIH HHS; P60 DK020572/DK/NIDDK NIH HHS; P60-DK20572/DK/NIDDK NIH HHS; R01 DK054222/DK/NIDDK NIH HHS; R01 DK065122/DK/NIDDK NIH HHS; R01 DK073601/DK/NIDDK NIH HHS; R01-DK065122/DK/NIDDK NIH HHS; R01-DK073601/DK/NIDDK NIH HHS; R01-DK54222/DK/NIDDK NIH HHS; T32 GM008322/GM/NIGMS NIH HHS; T32-GM008322/GM/NIGMS NIH HHS; //Medical Research Council
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/SH2B1 protein, human
Erratum In:
J Clin Invest. 2013 Jan 2;123(1):526
Note: Saeed, Sadia [added]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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