Browse by author
Lookup NU author(s): Professor Timothy Cheetham
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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 m 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.
Author(s): Doche ME, Bochukova EG, Su HW, Pearce LR, Keogh JM, Henning E, Cline JM, Dale A, Cheetham T, Barroso I, Argetsinger LS, O'Rahilly S, Rui LY, Carter-Su C, Farooqi IS
Publication type: Article
Publication status: Published
Journal: Journal of Clinical Investigation
Year: 2012
Volume: 122
Issue: 12
Pages: 4732-4736
Print publication date: 03/12/2012
ISSN (print): 0021-9738
ISSN (electronic): 1558-8238
Publisher: American Society for Clinical Investigation
URL: http://dx.doi.org/10.1172/JCI62696
DOI: 10.1172/JCI62696
Altmetrics provided by Altmetric
