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Chemical genetic screen for AMPKα2 substrates uncovers a network of proteins involved in mitosis.

Molecular cell | Dec 23, 2011

http://www.ncbi.nlm.nih.gov/pubmed/22137581

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.

Pubmed ID: 22137581 RIS Download

Mesh terms: AMP-Activated Protein Kinases | Adenosine Triphosphate | Cell Line, Tumor | Gene Expression Regulation, Enzymologic | HEK293 Cells | Humans | Mitosis | Myosin Light Chains | Phosphorylation | Protein Phosphatase 1 | Substrate Specificity | p21-Activated Kinases

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Associated grants

  • Agency: NIA NIH HHS, Id: AG026648
  • Agency: NIA NIH HHS, Id: AG032837
  • Agency: NIA NIH HHS, Id: AG31198
  • Agency: NIBIB NIH HHS, Id: EB001987
  • Agency: NIEHS NIH HHS, Id: ES153393
  • Agency: NIGMS NIH HHS, Id: GM068762
  • Agency: NHGRI NIH HHS, Id: HG3456
  • Agency: Medical Research Council, Id: MC_U127088492
  • Agency: NIA NIH HHS, Id: R01 AG031198
  • Agency: NIA NIH HHS, Id: R01 AG031198-01A1
  • Agency: NIA NIH HHS, Id: R01 AG031198-01A1S1
  • Agency: NIA NIH HHS, Id: R01 AG031198-02
  • Agency: NIA NIH HHS, Id: R01 AG031198-03
  • Agency: NIA NIH HHS, Id: R01 AG031198-04
  • Agency: NIGMS NIH HHS, Id: R01 GM056203
  • Agency: NCRR NIH HHS, Id: RR01614

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