KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation.
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ABSTRACT:
SUBMITTER: Pearce LR
PROVIDER: S-EPMC3898740 | biostudies-literature | 2013 Nov
REPOSITORIES: biostudies-literature
Publications
KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation.
Pearce Laura R LR Atanassova Neli N Banton Matthew C MC Bottomley Bill B van der Klaauw Agatha A AA Revelli Jean-Pierre JP Hendricks Audrey A Keogh Julia M JM Henning Elana E Doree Deon D Jeter-Jones Sabrina S Garg Sumedha S Bochukova Elena G EG Bounds Rebecca R Ashford Sofie S Gayton Emma E Hindmarsh Peter C PC Shield Julian P H JP Crowne Elizabeth E Barford David D Wareham Nick J NJ O'Rahilly Stephen S Murphy Michael P MP Powell David R DR Barroso Ines I Farooqi I Sadaf IS
Cell 20131101 4
Kinase suppressor of Ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. We explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and 1,536 controls. We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in tran ...[more]
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