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Ducommun, S.* ; Deak, M.* ; Zeigerer, A. ; Göransson, O.* ; Seitz, S. ; Collodet, C.* ; Madsen, A.B.* ; Jensen, T.E.* ; Viollet, B.* ; Foretz, M.* ; Gut, P.* ; Sumpton, D.* ; Sakamoto, K.*

Chemical genetic screen identifies Gapex-5/GAPVDI and STBD1 as novel AMPK substrates.

Cell. Signal. 57, 45-57 (2019)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
AMP-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis, acting as a sensor of energy and nutrient status. As such, AMPK is considered a promising drug target for treatment of medical conditions particularly associated with metabolic dysfunctions. To better understand the downstream effectors and physiological consequences of AMPK activation, we have employed a chemical genetic screen in mouse primary hepatocytes in an attempt to identify novel AMPK targets. Treatment of hepatocytes with a potent and specific AMPK activator 991 resulted in identification of 65 proteins phosphorylated upon AMPK activation, which are involved in a variety of cellular processes such as lipid/glycogen metabolism, vesicle trafficking, and cytoskeleton organisation. Further characterisation and validation using mass spectrometry followed by immunoblotting analysis with phosphorylation site-specific antibodies identified AMPK-dependent phosphorylation of Gapex-5 (also known as GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1)) on Ser902 in hepatocytes and starch-binding domain 1 (STBD1) on Ser175 in multiple cells/tissues. As new promising roles of AMPK as a key metabolic regulator continue to emerge, the substrates we identified could provide new mechanistic and therapeutic insights into AMPK-activating drugs in the liver.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Gtpase Activating Protein And Vps9 Domains 1 ; Shokat ; Starch-binding Domain 1; Activated Protein-kinase; Acetyl-coa Carboxylase; Skeletal-muscle; Fatty-acid; Glucose-uptake; Mitochondrial Fission; Insulin-resistance; Hepatic Steatosis; Glycogen-synthase; Molecular-cloning
ISSN (print) / ISBN 0898-6568
e-ISSN 0898-6568
Zeitschrift Cellular Signalling
Quellenangaben Band: 57, Heft: , Seiten: 45-57 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Cancer (IDC)