The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs

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Standard

The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs. / Dite, Toby A.; Ling, Naomi X.Y.; Scott, John W.; Hoque, Ashfaqul; Galic, Sandra; Parker, Benjamin L.; Ngoei, Kevin R.W.; Langendorf, Christopher G.; O'Brien, Matthew T.; Kundu, Mondira; Viollet, Benoit; Steinberg, Gregory R.; Sakamoto, Kei; Kemp, Bruce E.; Oakhill, Jonathan S.

I: Nature Communications, Bind 8, Nr. 1, 571, 01.12.2017.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Dite, TA, Ling, NXY, Scott, JW, Hoque, A, Galic, S, Parker, BL, Ngoei, KRW, Langendorf, CG, O'Brien, MT, Kundu, M, Viollet, B, Steinberg, GR, Sakamoto, K, Kemp, BE & Oakhill, JS 2017, 'The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs', Nature Communications, bind 8, nr. 1, 571. https://doi.org/10.1038/s41467-017-00628-y

APA

Dite, 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), [571]. https://doi.org/10.1038/s41467-017-00628-y

Vancouver

Dite TA, Ling NXY, Scott JW, Hoque A, Galic S, Parker BL o.a. The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs. Nature Communications. 2017 dec. 1;8(1). 571. https://doi.org/10.1038/s41467-017-00628-y

Author

Dite, Toby A. ; Ling, Naomi X.Y. ; Scott, John W. ; Hoque, Ashfaqul ; Galic, Sandra ; Parker, Benjamin L. ; Ngoei, Kevin R.W. ; Langendorf, Christopher G. ; O'Brien, Matthew T. ; Kundu, Mondira ; Viollet, Benoit ; Steinberg, Gregory R. ; Sakamoto, Kei ; Kemp, Bruce E. ; Oakhill, Jonathan S. / The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs. I: Nature Communications. 2017 ; Bind 8, Nr. 1.

Bibtex

@article{2ccedeb9a2a14c9c8d78cb947df464db,
title = "The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs",
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.",
author = "Dite, {Toby A.} and Ling, {Naomi X.Y.} and Scott, {John W.} and Ashfaqul Hoque and Sandra Galic and Parker, {Benjamin L.} and Ngoei, {Kevin R.W.} and Langendorf, {Christopher G.} and O'Brien, {Matthew T.} and Mondira Kundu and Benoit Viollet and Steinberg, {Gregory R.} and Kei Sakamoto and Kemp, {Bruce E.} and Oakhill, {Jonathan S.}",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/s41467-017-00628-y",
language = "English",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs

AU - Dite, Toby A.

AU - Ling, Naomi X.Y.

AU - Scott, John W.

AU - Hoque, Ashfaqul

AU - Galic, Sandra

AU - Parker, Benjamin L.

AU - Ngoei, Kevin R.W.

AU - Langendorf, Christopher G.

AU - O'Brien, Matthew T.

AU - Kundu, Mondira

AU - Viollet, Benoit

AU - Steinberg, Gregory R.

AU - Sakamoto, Kei

AU - Kemp, Bruce E.

AU - Oakhill, Jonathan S.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85029584631&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-00628-y

DO - 10.1038/s41467-017-00628-y

M3 - Journal article

C2 - 28924239

AN - SCOPUS:85029584631

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 571

ER -

ID: 238434510