The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs
Identifieur interne : 000C46 ( Pmc/Curation ); précédent : 000C45; suivant : 000C47The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs
Auteurs : Toby A. Dite ; Naomi X. Y. Ling ; John W. Scott ; Ashfaqul Hoque ; Sandra Galic ; Benjamin L. Parker [Australie] ; Kevin R. W. Ngoei ; Christopher G. Langendorf ; Matthew T. O Rien ; Mondira Kundu [États-Unis] ; Benoit Viollet [France] ; Gregory R. Steinberg ; Kei Sakamoto [Royaume-Uni, Suisse] ; Bruce E. Kemp ; Jonathan S. OakhillSource :
- Nature Communications [ 2041-1723 ] ; 2017.
Abstract
AMP-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.
Url:
DOI: 10.1038/s41467-017-00628-y
PubMed: 28924239
PubMed Central: 5603566
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Toby A. 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id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2194 1270</institution-id><institution-id institution-id-type="GRID">grid.411958.0</institution-id><institution>Mary MacKillop Institute for Health Research,</institution><institution>Australian Catholic University,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id 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Dite</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Metabolic Signalling Laboratory, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation></author><author><name sortKey="Ling, Naomi X Y" sort="Ling, Naomi X Y" uniqKey="Ling N" first="Naomi X. Y." last="Ling">Naomi X. Y. Ling</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Metabolic Signalling Laboratory, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation></author><author><name sortKey="Scott, John W" sort="Scott, John W" uniqKey="Scott J" first="John W." last="Scott">John W. Scott</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2194 1270</institution-id><institution-id institution-id-type="GRID">grid.411958.0</institution-id><institution>Mary MacKillop Institute for Health Research,</institution><institution>Australian Catholic University,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation></author><author><name sortKey="Hoque, Ashfaqul" sort="Hoque, Ashfaqul" uniqKey="Hoque A" first="Ashfaqul" last="Hoque">Ashfaqul Hoque</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Metabolic Signalling Laboratory, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation></author><author><name sortKey="Galic, Sandra" sort="Galic, Sandra" uniqKey="Galic S" first="Sandra" last="Galic">Sandra Galic</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation></author><author><name sortKey="Parker, Benjamin L" sort="Parker, Benjamin L" uniqKey="Parker B" first="Benjamin L." last="Parker">Benjamin L. Parker</name><affiliation wicri:level="2"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 834X</institution-id><institution-id institution-id-type="GRID">grid.1013.3</institution-id><institution>Charles Perkins Centre, School of Molecular Bioscience,</institution><institution>The University of Sydney,</institution></institution-wrap>Sydney, NSW Australia</nlm:aff><country>Australie</country><placeName><region type="state">Nouvelle-Galles du Sud</region></placeName><wicri:cityArea>Sydney</wicri:cityArea></affiliation></author><author><name sortKey="Ngoei, Kevin R W" sort="Ngoei, Kevin R W" uniqKey="Ngoei K" first="Kevin R. W." last="Ngoei">Kevin R. W. Ngoei</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation></author><author><name sortKey="Langendorf, Christopher G" sort="Langendorf, Christopher G" uniqKey="Langendorf C" first="Christopher G." last="Langendorf">Christopher G. Langendorf</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation></author><author><name sortKey="O Rien, Matthew T" sort="O Rien, Matthew T" uniqKey="O Rien M" first="Matthew T." last="O Rien">Matthew T. O Rien</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation></author><author><name sortKey="Kundu, Mondira" sort="Kundu, Mondira" uniqKey="Kundu M" first="Mondira" last="Kundu">Mondira Kundu</name><affiliation wicri:level="2"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0224 711X</institution-id><institution-id institution-id-type="GRID">grid.240871.8</institution-id><institution>Department of Pathology,</institution><institution>St Jude Children’s Research Hospital,</institution></institution-wrap>Memphis, TN USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea>Memphis</wicri:cityArea></affiliation></author><author><name sortKey="Viollet, Benoit" sort="Viollet, Benoit" uniqKey="Viollet B" first="Benoit" last="Viollet">Benoit Viollet</name><affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0643 431X</institution-id><institution-id institution-id-type="GRID">grid.462098.1</institution-id><institution>INSERM, U1016, Institut Cochin,</institution></institution-wrap>Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2112 9282</institution-id><institution-id institution-id-type="GRID">grid.4444.0</institution-id><institution>CNRS, UMR8104,</institution></institution-wrap>Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2188 0914</institution-id><institution-id institution-id-type="GRID">grid.10992.33</institution-id><institution>Université Paris Descartes, Sorbonne Paris Cité,</institution></institution-wrap>Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris</wicri:regionArea></affiliation></author><author><name sortKey="Steinberg, Gregory R" sort="Steinberg, Gregory R" uniqKey="Steinberg G" first="Gregory R." last="Steinberg">Gregory R. Steinberg</name><affiliation><nlm:aff id="Aff9"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8227</institution-id><institution-id institution-id-type="GRID">grid.25073.33</institution-id><institution>Divisions of Endocrinology and Metabolism, Department of Medicine, and Department of Biochemistry and Biomedical Sciences,</institution><institution>McMaster University,</institution></institution-wrap>Hamilton, ON Canada</nlm:aff><wicri:noCountry code="subfield">ON Canada</wicri:noCountry></affiliation></author><author><name sortKey="Sakamoto, Kei" sort="Sakamoto, Kei" uniqKey="Sakamoto K" first="Kei" last="Sakamoto">Kei Sakamoto</name><affiliation wicri:level="1"><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0397 2876</institution-id><institution-id institution-id-type="GRID">grid.8241.f</institution-id><institution>MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences,</institution><institution>University of Dundee,</institution></institution-wrap>Scotland, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Scotland</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff11"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0066 4948</institution-id><institution-id institution-id-type="GRID">grid.419905.0</institution-id><institution>Present Address: Nestlé Institute of Health Sciences SA,</institution></institution-wrap>Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Lausanne</wicri:regionArea></affiliation></author><author><name sortKey="Kemp, Bruce E" sort="Kemp, Bruce E" uniqKey="Kemp B" first="Bruce E." last="Kemp">Bruce E. Kemp</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2194 1270</institution-id><institution-id institution-id-type="GRID">grid.411958.0</institution-id><institution>Mary MacKillop Institute for Health Research,</institution><institution>Australian Catholic University,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation></author><author><name sortKey="Oakhill, Jonathan S" sort="Oakhill, Jonathan S" uniqKey="Oakhill J" first="Jonathan S." last="Oakhill">Jonathan S. Oakhill</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Metabolic Signalling Laboratory, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2194 1270</institution-id><institution-id institution-id-type="GRID">grid.411958.0</institution-id><institution>Mary MacKillop Institute for Health Research,</institution><institution>Australian Catholic University,</institution></institution-wrap>Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">AMP-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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hardie, Dg" uniqKey="Hardie D">DG Hardie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Steinberg, Gr" uniqKey="Steinberg G">GR Steinberg</name></author><author><name sortKey="Kemp, Be" uniqKey="Kemp B">BE Kemp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oakhill, Js" uniqKey="Oakhill J">JS Oakhill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Houde, Vp" uniqKey="Houde V">VP Houde</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xiao, B" uniqKey="Xiao B">B Xiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oakhill, Js" uniqKey="Oakhill J">JS Oakhill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hawley, Sa" uniqKey="Hawley S">SA Hawley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scott, Jw" uniqKey="Scott J">JW Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Langendorf, Cg" uniqKey="Langendorf C">CG Langendorf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sanders, Mj" uniqKey="Sanders M">MJ Sanders</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xiao, B" uniqKey="Xiao B">B Xiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scott, Jw" uniqKey="Scott J">JW Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Calabrese, Mf" uniqKey="Calabrese M">MF Calabrese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hawley, Sa" uniqKey="Hawley S">SA Hawley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scott, Jw" uniqKey="Scott J">JW Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scott, Jw" uniqKey="Scott J">JW Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oakhill, Js" uniqKey="Oakhill J">JS Oakhill</name></author><author><name sortKey="Scott, Jw" uniqKey="Scott J">JW Scott</name></author><author><name sortKey="Kemp, Be" uniqKey="Kemp B">BE Kemp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T Suzuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loffler, As" uniqKey="Loffler A">AS Löffler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mitchelhill, Ki" uniqKey="Mitchelhill K">KI Mitchelhill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Eill, Hm" uniqKey="O Eill H">HM O’Neill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Laderoute, Kr" uniqKey="Laderoute K">KR Laderoute</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Egan, Df" uniqKey="Egan D">DF Egan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Truong, Th" uniqKey="Truong T">TH Truong</name></author><author><name sortKey="Carroll, Ks" uniqKey="Carroll K">KS Carroll</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Erickson, Jr" uniqKey="Erickson J">JR Erickson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Humphries, Km" uniqKey="Humphries K">KM Humphries</name></author><author><name sortKey="Deal, Ms" uniqKey="Deal M">MS Deal</name></author><author><name sortKey="Taylor, Ss" uniqKey="Taylor S">SS Taylor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cosentino Gomes, D" uniqKey="Cosentino Gomes D">D Cosentino-Gomes</name></author><author><name sortKey="Rocco Machado, N" uniqKey="Rocco Machado N">N Rocco-Machado</name></author><author><name sortKey="Meyer Fernandes, Jr" uniqKey="Meyer Fernandes J">JR Meyer-Fernandes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheong, H" uniqKey="Cheong H">H Cheong</name></author><author><name sortKey="Lindsten, T" uniqKey="Lindsten T">T Lindsten</name></author><author><name sortKey="Wu, J" uniqKey="Wu J">J Wu</name></author><author><name sortKey="Lu, C" uniqKey="Lu C">C Lu</name></author><author><name sortKey="Thompson, Cb" uniqKey="Thompson C">CB Thompson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Y L" uniqKey="Zhang Y">Y-L Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liang, J" uniqKey="Liang J">J Liang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Egan, Df" uniqKey="Egan D">DF Egan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ford, Rj" uniqKey="Ford R">RJ Ford</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Rien, Aj" uniqKey="O Rien A">AJ O’Brien</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fullerton, Md" uniqKey="Fullerton M">MD Fullerton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zadra, G" uniqKey="Zadra G">G Zadra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cameron, Ko" uniqKey="Cameron K">KO Cameron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shackleford, Db" uniqKey="Shackleford D">DB Shackleford</name></author><author><name sortKey="Shaw, Rj" uniqKey="Shaw R">RJ Shaw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wojtaszewski, Jf" uniqKey="Wojtaszewski J">JF Wojtaszewski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="J Rgensen, Sb" uniqKey="J Rgensen S">SB Jørgensen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dzamko, N" uniqKey="Dzamko N">N Dzamko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schwalm, C" uniqKey="Schwalm C">C Schwalm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alexander, A" uniqKey="Alexander A">A Alexander</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, S C" uniqKey="Zhang S">S-C Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jung, Jh" uniqKey="Jung J">JH Jung</name></author><author><name sortKey="Traugh, Ja" uniqKey="Traugh J">JA Traugh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jakobi, R" uniqKey="Jakobi R">R Jakobi</name></author><author><name sortKey="Moertl, E" uniqKey="Moertl E">E Moertl</name></author><author><name sortKey="Koeppel, Ma" uniqKey="Koeppel M">MA Koeppel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kundu, M" uniqKey="Kundu M">M Kundu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mitter, Sk" uniqKey="Mitter S">SK Mitter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Behrends, C" uniqKey="Behrends C">C Behrends</name></author><author><name sortKey="Sowa, Me" uniqKey="Sowa M">ME Sowa</name></author><author><name sortKey="Gygi, Sp" uniqKey="Gygi S">SP Gygi</name></author><author><name sortKey="Harper, Jw" uniqKey="Harper J">JW Harper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hardie, Dg" uniqKey="Hardie D">DG Hardie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Russell, Rc" uniqKey="Russell R">RC Russell</name></author><author><name sortKey="Yuan, Hx" uniqKey="Yuan H">HX Yuan</name></author><author><name sortKey="Guan, Kl" uniqKey="Guan K">KL Guan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, W" uniqKey="Wu W">W Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, J" uniqKey="Kim J">J Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Davies, M" uniqKey="Davies M">M Davies</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boersema, Pj" uniqKey="Boersema P">PJ Boersema</name></author><author><name sortKey="Raijmakers, R" uniqKey="Raijmakers R">R Raijmakers</name></author><author><name sortKey="Lemeer, S" uniqKey="Lemeer S">S Lemeer</name></author><author><name sortKey="Mohammed, S" uniqKey="Mohammed S">S Mohammed</name></author><author><name sortKey="Heck, Aj" uniqKey="Heck A">AJ Heck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thingholm, Te" uniqKey="Thingholm T">TE Thingholm</name></author><author><name sortKey="Jorgensen, Tj" uniqKey="Jorgensen T">TJ Jorgensen</name></author><author><name sortKey="Jensen, On" uniqKey="Jensen O">ON Jensen</name></author><author><name sortKey="Larsen, Mr" uniqKey="Larsen M">MR Larsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tyanova, S" uniqKey="Tyanova S">S Tyanova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cox, J" uniqKey="Cox J">J Cox</name></author><author><name sortKey="Mann, M" uniqKey="Mann M">M Mann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vizcaino, Ja" uniqKey="Vizcaino J">JA Vizcaíno</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id><journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id><journal-title-group><journal-title>Nature Communications</journal-title></journal-title-group><issn pub-type="epub">2041-1723</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28924239</article-id><article-id pub-id-type="pmc">5603566</article-id><article-id pub-id-type="publisher-id">628</article-id><article-id pub-id-type="doi">10.1038/s41467-017-00628-y</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Dite</surname><given-names>Toby A.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Ling</surname><given-names>Naomi X. Y.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Scott</surname><given-names>John W.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Hoque</surname><given-names>Ashfaqul</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Galic</surname><given-names>Sandra</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Parker</surname><given-names>Benjamin L.</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ngoei</surname><given-names>Kevin R. W.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Langendorf</surname><given-names>Christopher G.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>O’Brien</surname><given-names>Matthew T.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kundu</surname><given-names>Mondira</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-0121-0224</contrib-id><name><surname>Viollet</surname><given-names>Benoit</given-names></name><xref ref-type="aff" rid="Aff6">6</xref><xref ref-type="aff" rid="Aff7">7</xref><xref ref-type="aff" rid="Aff8">8</xref></contrib><contrib contrib-type="author"><name><surname>Steinberg</surname><given-names>Gregory R.</given-names></name><xref ref-type="aff" rid="Aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>Sakamoto</surname><given-names>Kei</given-names></name><xref ref-type="aff" rid="Aff10">10</xref><xref ref-type="aff" rid="Aff11">11</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-6735-5082</contrib-id><name><surname>Kemp</surname><given-names>Bruce E.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Oakhill</surname><given-names>Jonathan S.</given-names></name><address><email>joakhill@svi.edu.au</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Metabolic Signalling Laboratory, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2179 088X</institution-id><institution-id institution-id-type="GRID">grid.1008.9</institution-id><institution>Protein Chemistry & Metabolism, St Vincent’s Institute of Medical Research,</institution><institution>University of Melbourne,</institution></institution-wrap>Melbourne, VIC Australia</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2194 1270</institution-id><institution-id institution-id-type="GRID">grid.411958.0</institution-id><institution>Mary MacKillop Institute for Health Research,</institution><institution>Australian Catholic University,</institution></institution-wrap>Melbourne, VIC Australia</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 834X</institution-id><institution-id institution-id-type="GRID">grid.1013.3</institution-id><institution>Charles Perkins Centre, School of Molecular Bioscience,</institution><institution>The University of Sydney,</institution></institution-wrap>Sydney, NSW Australia</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0224 711X</institution-id><institution-id institution-id-type="GRID">grid.240871.8</institution-id><institution>Department of Pathology,</institution><institution>St Jude Children’s Research Hospital,</institution></institution-wrap>Memphis, TN USA</aff><aff id="Aff6"><label>6</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0643 431X</institution-id><institution-id institution-id-type="GRID">grid.462098.1</institution-id><institution>INSERM, U1016, Institut Cochin,</institution></institution-wrap>Paris, France</aff><aff id="Aff7"><label>7</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2112 9282</institution-id><institution-id institution-id-type="GRID">grid.4444.0</institution-id><institution>CNRS, UMR8104,</institution></institution-wrap>Paris, France</aff><aff id="Aff8"><label>8</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2188 0914</institution-id><institution-id institution-id-type="GRID">grid.10992.33</institution-id><institution>Université Paris Descartes, Sorbonne Paris Cité,</institution></institution-wrap>Paris, France</aff><aff id="Aff9"><label>9</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8227</institution-id><institution-id institution-id-type="GRID">grid.25073.33</institution-id><institution>Divisions of Endocrinology and Metabolism, Department of Medicine, and Department of Biochemistry and Biomedical Sciences,</institution><institution>McMaster University,</institution></institution-wrap>Hamilton, ON Canada</aff><aff id="Aff10"><label>10</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0397 2876</institution-id><institution-id institution-id-type="GRID">grid.8241.f</institution-id><institution>MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences,</institution><institution>University of Dundee,</institution></institution-wrap>Scotland, UK</aff><aff id="Aff11"><label>11</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0066 4948</institution-id><institution-id institution-id-type="GRID">grid.419905.0</institution-id><institution>Present Address: Nestlé Institute of Health Sciences SA,</institution></institution-wrap>Lausanne, Switzerland</aff></contrib-group><pub-date pub-type="epub"><day>18</day><month>9</month><year>2017</year></pub-date><pub-date pub-type="pmc-release"><day>18</day><month>9</month><year>2017</year></pub-date><pub-date pub-type="collection"><year>2017</year></pub-date><volume>8</volume><elocation-id>571</elocation-id><history><date date-type="received"><day>27</day><month>9</month><year>2016</year></date><date date-type="accepted"><day>14</day><month>7</month><year>2017</year></date></history><permissions><copyright-statement>© The Author(s) 2017</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">AMP-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.</p></abstract><abstract id="Abs2" abstract-type="web-summary"><p id="Par2">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.</p></abstract><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2017</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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