Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates

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Standard

Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates. / Ducommun, Serge; Deak, Maria; Zeigerer, Anja; Göransson, Olga; Seitz, Susanne; Collodet, Caterina; Madsen, Agnete Bjerregaard; Jensen, Thomas Elbenhardt; Viollet, Benoit; Foretz, Marc; Gut, Philipp; Sumpton, David; Sakamoto, Kei.

I: Cellular Signalling, Bind 57, 2019, s. 45-57.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Ducommun, S, Deak, M, Zeigerer, A, Göransson, O, Seitz, S, Collodet, C, Madsen, AB, Jensen, TE, Viollet, B, Foretz, M, Gut, P, Sumpton, D & Sakamoto, K 2019, 'Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates', Cellular Signalling, bind 57, s. 45-57. https://doi.org/10.1016/j.cellsig.2019.02.001

APA

Ducommun, S., Deak, M., Zeigerer, A., Göransson, O., Seitz, S., Collodet, C., ... Sakamoto, K. (2019). Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates. Cellular Signalling, 57, 45-57. https://doi.org/10.1016/j.cellsig.2019.02.001

Vancouver

Ducommun S, Deak M, Zeigerer A, Göransson O, Seitz S, Collodet C o.a. Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates. Cellular Signalling. 2019;57:45-57. https://doi.org/10.1016/j.cellsig.2019.02.001

Author

Ducommun, Serge ; Deak, Maria ; Zeigerer, Anja ; Göransson, Olga ; Seitz, Susanne ; Collodet, Caterina ; Madsen, Agnete Bjerregaard ; Jensen, Thomas Elbenhardt ; Viollet, Benoit ; Foretz, Marc ; Gut, Philipp ; Sumpton, David ; Sakamoto, Kei. / Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates. I: Cellular Signalling. 2019 ; Bind 57. s. 45-57.

Bibtex

@article{786aebf1aab14fcfaee6180975d97388,
title = "Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates",
abstract = "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 organization. Further characterization 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.",
keywords = "Faculty of Science, GTPase activating protein and VPS9 domains 1, Shokat, Starch-binding domain 1",
author = "Serge Ducommun and Maria Deak and Anja Zeigerer and Olga G{\"o}ransson and Susanne Seitz and Caterina Collodet and Madsen, {Agnete Bjerregaard} and Jensen, {Thomas Elbenhardt} and Benoit Viollet and Marc Foretz and Philipp Gut and David Sumpton and Kei Sakamoto",
note = "CURIS 2019 NEXS 073 Copyright {\circledC} 2019. Published by Elsevier Inc.",
year = "2019",
doi = "10.1016/j.cellsig.2019.02.001",
language = "English",
volume = "57",
pages = "45--57",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates

AU - Ducommun, Serge

AU - Deak, Maria

AU - Zeigerer, Anja

AU - Göransson, Olga

AU - Seitz, Susanne

AU - Collodet, Caterina

AU - Madsen, Agnete Bjerregaard

AU - Jensen, Thomas Elbenhardt

AU - Viollet, Benoit

AU - Foretz, Marc

AU - Gut, Philipp

AU - Sumpton, David

AU - Sakamoto, Kei

N1 - CURIS 2019 NEXS 073 Copyright © 2019. Published by Elsevier Inc.

PY - 2019

Y1 - 2019

N2 - 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 organization. Further characterization 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.

AB - 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 organization. Further characterization 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.

KW - Faculty of Science

KW - GTPase activating protein and VPS9 domains 1

KW - Shokat

KW - Starch-binding domain 1

U2 - 10.1016/j.cellsig.2019.02.001

DO - 10.1016/j.cellsig.2019.02.001

M3 - Journal article

C2 - 30772465

VL - 57

SP - 45

EP - 57

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

ER -

ID: 213663914