PuSH - Publikationsserver des Helmholtz Zentrums München

Costanzo-Garvey, D.L.* ; Pfluger, P.T.* ; Dougherty, M.K.* ; Stock, J.L.* ; Boehm, M.* ; Chaika, O.* ; Fernandez, M.R.* ; Fisher, K.* ; Kortum, R.L.* ; Hong, E.G.* ; Jun, J.Y.* ; Ko, H.J.* ; Schreiner, A.* ; Volle, D.J.* ; Treece, T.* ; Swift, A.L.* ; Winer, M.* ; Chen, D.* ; Wu, M.* ; Leon, L.R.* ; Shaw, A.S.* ; McNeish, J.* ; Kim, J.K.* ; Morrison, D.K.* ; Tschöp, M.H.* ; Lewis, R.E.*

KSR2 is an essential regulator of AMP kinase, energy expenditure, and insulin sensitivity.

Cell Metab. 10, 366-78 (2009)
DOI Verlagsversion bestellen
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Zeitschrift Cell Metabolism
Quellenangaben Band: 10, Heft: 5, Seiten: 366-78 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed