Chemical Genetic Screen for AMPKα2 Substrates Uncovers a Network of Proteins Involved in Mitosis
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Banko-2011-Chemical Genetic Scr.pdf
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Author(s)
Banko, Max R.
Allen, Jasmina J.
Schaffer, Bethany E.
Wilker, Erik W.
Tsou, Peiling
White, Jamie L.
Villen, Judit
Wang, Beatrice
Kim, Sara R.
Sakamoto, Kei
Date Issued
December 2011
Journal
Molecular Cell
Publisher
Elsevier
Citation
Banko, Max R., Jasmina J. Allen, Bethany E. Schaffer, Erik W. Wilker, Peiling Tsou, Jamie L. White, Judit Villén, et al. “Chemical Genetic Screen for AMPKα2 Substrates Uncovers a Network of Proteins Involved in Mitosis.” Molecular Cell 44, no. 6 (December 2011): 878–892. © 2011 Elsevier Inc.
Version
Final published version
Abstract
The energy-sensing AMP-activated protein kinase (AMPK) is activated by low nutrient levels. Functions of AMPK, other than its role in cellular metabolism, are just beginning to emerge. Here we use a chemical genetics screen to identify direct substrates of AMPK in human cells. We find that AMPK phosphorylates 28 previously unidentified substrates, several of which are involved in mitosis and cytokinesis. We identify the residues phosphorylated by AMPK in vivo in several substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and p21-activated protein kinase (PAK2). AMPK-induced phosphorylation is necessary for PPP1R12C interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both AMPK activity and PPP1R12C phosphorylation are increased in mitotic cells and are important for mitosis completion. These findings suggest that AMPK coordinates nutrient status with mitosis completion, which may be critical for the organism's response to low nutrients during development, or in adult stem and cancer cells.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2011.11.005
