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dc.contributor.authorDite, TA
dc.contributor.authorLing, NXY
dc.contributor.authorScott, JW
dc.contributor.authorHoque, A
dc.contributor.authorGalic, S
dc.contributor.authorParker, BL
dc.contributor.authorNgoei, KRW
dc.contributor.authorLangendorf, CG
dc.contributor.authorO'Brien, MT
dc.contributor.authorKundu, M
dc.contributor.authorViollet, B
dc.contributor.authorSteinberg, GR
dc.contributor.authorSakamoto, K
dc.contributor.authorKemp, BE
dc.contributor.authorOakhill, JS
dc.date.accessioned2020-12-21T02:41:39Z
dc.date.available2020-12-21T02:41:39Z
dc.date.issued2017-09-18
dc.identifierpii: 10.1038/s41467-017-00628-y
dc.identifier.citationDite, T. A., Ling, N. X. Y., Scott, J. W., Hoque, A., Galic, S., Parker, B. L., Ngoei, K. R. W., Langendorf, C. G., O'Brien, M. T., Kundu, M., Viollet, B., Steinberg, G. R., Sakamoto, K., Kemp, B. E. & Oakhill, J. S. (2017). The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs. NATURE COMMUNICATIONS, 8 (1), https://doi.org/10.1038/s41467-017-00628-y.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/257031
dc.description.abstractAMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for maintaining cellular energy homeostasis. Activation of AMPK by salicylate and the thienopyridone A-769662 is critically dependent on phosphorylation of Ser108 in the β1 regulatory subunit. Here, we show a possible role for Ser108 phosphorylation in cell cycle regulation and promotion of pro-survival pathways in response to energy stress. We identify the autophagy initiator Unc-51-like kinase 1 (ULK1) as a β1-Ser108 kinase in cells. Cellular β1-Ser108 phosphorylation by ULK1 was dependent on AMPK β-subunit myristoylation, metabolic stress associated with elevated AMP/ATP ratio, and the intrinsic energy sensing capacity of AMPK; features consistent with an AMP-induced myristoyl switch mechanism. We further demonstrate cellular AMPK signaling independent of activation loop Thr172 phosphorylation, providing potential insight into physiological roles for Ser108 phosphorylation. These findings uncover new mechanisms by which AMPK could potentially maintain cellular energy homeostasis independently of Thr172 phosphorylation.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.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleThe autophagy initiator ULK1 sensitizes AMPK to allosteric drugs
dc.typeJournal Article
dc.identifier.doi10.1038/s41467-017-00628-y
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.affiliation.departmentBio21
melbourne.affiliation.departmentMedicine (St Vincent's)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.affiliation.facultyAffiliate
melbourne.source.titleNature Communications
melbourne.source.volume8
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1238633
melbourne.contributor.authorSteinberg, Gregory
melbourne.contributor.authorDite, Toby
melbourne.contributor.authorHoque, Md Ashfaqul
melbourne.contributor.authorKemp, Bruce
melbourne.contributor.authorOakhill, Jonathan
melbourne.contributor.authorNgoei, Kevin
melbourne.contributor.authorScott, John
melbourne.contributor.authorGalic, Sandra
melbourne.contributor.authorParker, Benjamin
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


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