The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs

Toby A. Dite; Naomi X. Y. Ling; John W. Scott; Ashfaqul Hoque; Sandra Galic; Benjamin L. Parker; Kevin R. W. Ngoei; Christopher G. Langendorf; Matthew T. O’Brien; Mondira Kundu; Benoit Viollet; Gregory R. Steinberg; Kei Sakamoto; Bruce E. Kemp; Jonathan S. Oakhill

doi:10.1038/s41467-017-00628-y

Nature Communications (Sep 2017)

The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs

Toby A. Dite,
Naomi X. Y. Ling,
John W. Scott,
Ashfaqul Hoque,
Sandra Galic,
Benjamin L. Parker,
Kevin R. W. Ngoei,
Christopher G. Langendorf,
Matthew T. O’Brien,
Mondira Kundu,
Benoit Viollet,
Gregory R. Steinberg,
Kei Sakamoto,
Bruce E. Kemp,
Jonathan S. Oakhill

Affiliations

Toby A. Dite: Metabolic Signalling Laboratory, St Vincent’s Institute of Medical Research, University of Melbourne
Naomi X. Y. Ling: Metabolic Signalling Laboratory, St Vincent’s Institute of Medical Research, University of Melbourne
John W. Scott: Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research, University of Melbourne
Ashfaqul Hoque: Metabolic Signalling Laboratory, St Vincent’s Institute of Medical Research, University of Melbourne
Sandra Galic: Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research, University of Melbourne
Benjamin L. Parker: Charles Perkins Centre, School of Molecular Bioscience, The University of Sydney
Kevin R. W. Ngoei: Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research, University of Melbourne
Christopher G. Langendorf: Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research, University of Melbourne
Matthew T. O’Brien: Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research, University of Melbourne
Mondira Kundu: Department of Pathology, St Jude Children’s Research Hospital
Benoit Viollet: INSERM, U1016, Institut Cochin
Gregory R. Steinberg: Divisions of Endocrinology and Metabolism, Department of Medicine, and Department of Biochemistry and Biomedical Sciences, McMaster University
Kei Sakamoto: MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee
Bruce E. Kemp: Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research, University of Melbourne
Jonathan S. Oakhill: Metabolic Signalling Laboratory, St Vincent’s Institute of Medical Research, University of Melbourne

DOI: https://doi.org/10.1038/s41467-017-00628-y
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 14

Abstract

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AMPK is involved in sensing of metabolic stress. The authors show that the autophagy initiator ULK1 phosphorylates β1-Ser108 on the regulatory β1-subunit, sensitizing AMPK to allosteric drugs, and activates signaling pathways that appear independent of Thr172 phosphorylation in the kinase activation loop.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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