| First Author | Costanzo-Garvey DL | Year | 2009 |
| Journal | Cell Metab | Volume | 10 |
| Issue | 5 | Pages | 366-78 |
| PubMed ID | 19883615 | Mgi Jnum | J:155434 |
| Mgi Id | MGI:4413650 | Doi | 10.1016/j.cmet.2009.09.010 |
| Citation | Costanzo-Garvey DL, et al. (2009) KSR2 is an essential regulator of AMP kinase, energy expenditure, and insulin sensitivity. Cell Metab 10(5):366-78 |
| 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. |
