| Literature DB >> 19883615 |
Diane L Costanzo-Garvey1, Paul T Pfluger, Michele K Dougherty, Jeffery L Stock, Matthew Boehm, Oleg Chaika, Mario R Fernandez, Kurt Fisher, Robert L Kortum, Eun-Gyoung Hong, John Y Jun, Hwi Jin Ko, Aimee Schreiner, Deanna J Volle, Tina Treece, Amy L Swift, Mike Winer, Denise Chen, Min Wu, Lisa R Leon, Andrey S Shaw, John McNeish, Jason K Kim, Deborah K Morrison, Matthias H Tschöp, Robert E Lewis.
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(-/-) mice are hypophagic and hyperactive but expend less energy than wild-type mice. In addition, hyperinsulinemic-euglycemic clamp studies reveal that ksr2(-/-) mice are profoundly insulin resistant. The expression of genes mediating oxidative phosphorylation is also downregulated in the adipose tissue of ksr2(-/-) mice. These data demonstrate that ksr2(-/-) mice are highly efficient in conserving energy, revealing a novel role for KSR2 in AMPK-mediated regulation of energy metabolism.Entities:
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Year: 2009 PMID： 19883615 PMCID： PMC2773684 DOI： 10.1016/j.cmet.2009.09.010
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287