Accession Number:

ADA523500

Title:

KSR2 Is an Essential Regulator of AMP Kinase, Energy Expenditure, and Insulin Sensitivity

Descriptive Note:

Journal article

Corporate Author:

ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA THERMAL AND MOUNTAIN MEDICINE DIVISION

Report Date:

2009-11-04

Pagination or Media Count:

14.0

Abstract:

Kinase suppressors of Ras 1 and 2 KSR1 and KSR2 function as molecular scaffolds to potently regulate the MAP kinases ERK12 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.

Subject Categories:

  • Biochemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE