Abstract
Originalsprog | Engelsk |
---|---|
Tidsskrift | Diabetes |
Vol/bind | 55 |
Udgave nummer | 7 |
Sider (fra-til) | 2051-8 |
Antal sider | 7 |
ISSN | 0012-1797 |
DOI | |
Status | Udgivet - 2006 |
Bibliografisk note
Keywords: Adenylate Kinase; Aminoimidazole Carboxamide; Animals; Biological Transport; Catalysis; GTPase-Activating Proteins; Glucose; Insulin; Kinetics; Mice; Mice, Knockout; Muscle, Skeletal; Phosphorylation; Protein Subunits; RibonucleotidesAdgang til dokumentet
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AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits. / Treebak, Jonas T; Glund, Stephan; Deshmukh, Atul; Klein, Ditte K; Long, Yun Chau; Jensen, Thomas E; Jørgensen, Sebastian B; Viollet, Benoit; Andersson, Leif; Neumann, Dietbert; Wallimann, Theo; Richter, Erik A; Chibalin, Alexander V; Zierath, Juleen R; Wojtaszewski, Jørgen F P.
I: Diabetes, Bind 55, Nr. 7, 2006, s. 2051-8.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.
AU - Treebak, Jonas T
AU - Glund, Stephan
AU - Deshmukh, Atul
AU - Klein, Ditte K
AU - Long, Yun Chau
AU - Jensen, Thomas E
AU - Jørgensen, Sebastian B
AU - Viollet, Benoit
AU - Andersson, Leif
AU - Neumann, Dietbert
AU - Wallimann, Theo
AU - Richter, Erik A
AU - Chibalin, Alexander V
AU - Zierath, Juleen R
AU - Wojtaszewski, Jørgen F P
N1 - Keywords: Adenylate Kinase; Aminoimidazole Carboxamide; Animals; Biological Transport; Catalysis; GTPase-Activating Proteins; Glucose; Insulin; Kinetics; Mice; Mice, Knockout; Muscle, Skeletal; Phosphorylation; Protein Subunits; Ribonucleotides
PY - 2006
Y1 - 2006
N2 - AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR). AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake. We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle. Recombinant AMPK heterotrimeric complexes (alpha1beta1gamma1 and alpha2beta2gamma1) phosphorylate AS160 in a cell-free assay. In mice deficient in AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle. Contraction-mediated AS160 phosphorylation was also impaired in alpha2 AMPK KO and KD but not gamma3 AMPK KO mice. Our results implicate AS160 as a downstream target of AMPK.
AB - AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR). AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake. We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle. Recombinant AMPK heterotrimeric complexes (alpha1beta1gamma1 and alpha2beta2gamma1) phosphorylate AS160 in a cell-free assay. In mice deficient in AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle. Contraction-mediated AS160 phosphorylation was also impaired in alpha2 AMPK KO and KD but not gamma3 AMPK KO mice. Our results implicate AS160 as a downstream target of AMPK.
U2 - 10.2337/db06-0175
DO - 10.2337/db06-0175
M3 - Journal article
C2 - 16804075
VL - 55
SP - 2051
EP - 2058
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 7
ER -