PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
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)
Publ. Version/Full Text DOI PMC
Open Access Hybrid
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
3.388
0.862
9
11
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords 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
Language english
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 0898-6568
e-ISSN 0898-6568
Journal Cellular Signalling
Quellenangaben Volume: 57, Issue: , Pages: 45-57 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-501900-254
DOI 10.1016/j.cellsig.2019.02.001
WOS ID WOS:000462104300006
Scopus ID 85061782847
PubMed ID 30772465
Erfassungsdatum 2019-03-11
[➜Report correction]