|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2009-11-3
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
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.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
1932-7420
|
|
pubmed:author |
pubmed-author:BoehmMatthewM,
pubmed-author:ChaikaOlegO,
pubmed-author:ChenDeniseD,
pubmed-author:Costanzo-GarveyDiane LDL,
pubmed-author:DoughertyMichele KMK,
pubmed-author:FernandezMario RMR,
pubmed-author:FisherKurtK,
pubmed-author:HongEun-GyoungEG,
pubmed-author:JunJohn YJY,
pubmed-author:KimJason KJK,
pubmed-author:KoHwi JinHJ,
pubmed-author:KortumRobert LRL,
pubmed-author:LeonLisa RLR,
pubmed-author:LewisRobert ERE,
pubmed-author:McNeishJohnJ,
pubmed-author:MorrisonDeborah KDK,
pubmed-author:PflugerPaul TPT,
pubmed-author:SchreinerAimeeA,
pubmed-author:ShawAndrey SAS,
pubmed-author:StockJeffery LJL,
pubmed-author:SwiftAmy LAL,
pubmed-author:TreeceTinaT,
pubmed-author:TschöpMatthias HMH,
pubmed-author:VolleDeanna JDJ,
pubmed-author:WinerMikeM,
pubmed-author:WuMinM
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
10
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
366-78
|
|
pubmed:dateRevised |
2011-8-1
|
|
pubmed:meshHeading |
pubmed-meshheading:19883615-AMP-Activated Protein Kinases,
pubmed-meshheading:19883615-Adipose Tissue,
pubmed-meshheading:19883615-Animals,
pubmed-meshheading:19883615-COS Cells,
pubmed-meshheading:19883615-Cells, Cultured,
pubmed-meshheading:19883615-Cercopithecus aethiops,
pubmed-meshheading:19883615-Energy Metabolism,
pubmed-meshheading:19883615-Fatty Acids,
pubmed-meshheading:19883615-Glucose,
pubmed-meshheading:19883615-Glycolysis,
pubmed-meshheading:19883615-Insulin Resistance,
pubmed-meshheading:19883615-MAP Kinase Signaling System,
pubmed-meshheading:19883615-Mice,
pubmed-meshheading:19883615-Mice, Knockout,
pubmed-meshheading:19883615-Obesity,
pubmed-meshheading:19883615-Oxidation-Reduction,
pubmed-meshheading:19883615-Oxidative Phosphorylation,
pubmed-meshheading:19883615-Protein-Serine-Threonine Kinases,
pubmed-meshheading:19883615-Thermogenesis
|
|
pubmed:year |
2009
|
|
pubmed:articleTitle |
KSR2 is an essential regulator of AMP kinase, energy expenditure, and insulin sensitivity.
|
|
pubmed:affiliation |
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-7696, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
