KSR2 Is an Essential Regulator of AMP Kinase, Energy Expenditure, and Insulin Sensitivity
Abstract
Kinase suppressors of Ras 1 and 2 (KSR1 and KSR2) function as molecular scaffolds to potently regulate the MAP kinases ERK1/2 and affect multiple cell fates. Here we show that KSR2 interacts with and modulates the activity of AMPK. KSR2 regulates AMPK-dependent glucose uptake and fatty acid oxidation in mouse embryonic fibroblasts and glycolysis in a neuronal cell line. Disruption of KSR2 in vivo impairs AMPK-regulated processes affecting fatty acid oxidation and thermogenesis to cause obesity. Despite their increased adiposity, ksr2-1- mice are hypophagic and hyperactive but expend less energy than wild-type mice. In addition, hyperinsulinemiceuglycemic clamp studies reveal that ksr2-1- mice are profoundly insulin resistant. The expression of genes mediating oxidative phosphorylation is also downregulated in the adipose tissue of ksr2-1- mice. These data demonstrate that ksr2-1- mice are highly efficient in conserving energy, revealing a novel role for KSR2 in AMPK-mediated regulation of energy metabolism.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 04, 2009
- Accession Number
- ADA523500
Entities
People
- Aimee Schreiner
- Amy L. Swift
- Deanna J. Volle
- Denise Chen
- Diane L. Costanzo-garvey
- Eun-gyoung Hong
- Hwi J. Ko
- Jeffery L. Stock
- John Y. Jun
- Kurt Fisher
- Lisa R. Leon
- Mario R. Fernandez
- Matthew Boehm
- Michael Winer
- Michele K. Dougherty
- Min Wu
- Oleg Chaika
- Paul T. Pfluger
- Robert L Kortum
- Tine Treece
Organizations
- United States Army Research Institute of Environmental Medicine