Dataset Information

Quantitative global and phosphoproteomic analysis to define the cellular role of AMPK β1-Ser108 phosphorylation

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. We identified the autophagy initiator Unc-51-like kinase 1 (ULK1) as a β1-Ser108 kinase. ULK1 phosphorylation was specific to the β1-isoform and sensitised AMPK to salicylate and A-769662. To investigate the cellular fate of β1-Ser108 phosphorylation, we performed a stable isotope dimethyl labelling-based quantitative proteomic and phosphoproteomic analysis using lentivirus-transduced S108A and S108E mutants of β1 in β1/2-dKO iMEFs cells. Following 1 h phenformin (2 mM) treatment, β1-S108A and β1-S108E transduced iMEF lysates were compared to trace out the changes in proteome and phosphoprotome to decipher the possible cellular role of β1-Ser108 phosphorylation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Ashfaqul Hoque

LAB HEAD: Jonathan S. Oakhill

PROVIDER: PXD006365 | Pride | 2018-10-24

REPOSITORIES: Pride

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Publications

The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs.

Dite Toby A TA Ling Naomi X Y NXY Scott John W JW Hoque Ashfaqul A Galic Sandra S Parker Benjamin L BL Ngoei Kevin R W KRW Langendorf Christopher G CG O'Brien Matthew T MT Kundu Mondira M Viollet Benoit B Steinberg Gregory R GR Sakamoto Kei K Kemp Bruce E BE Oakhill Jonathan S JS

Nature communications 20170918 1

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 ...[more]

PMID: 28924239

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Dataset Information

Quantitative global and phosphoproteomic analysis to define the cellular role of AMPK β1-Ser108 phosphorylation

Publications

The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs.

Similar Datasets

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