PP2A regulatory subunit PP2A-B' counteracts S6K phosphorylation

Cell Metab. 2010 May 5;11(5):438-44. doi: 10.1016/j.cmet.2010.03.015.


The insulin/TOR signaling pathway plays a crucial role in animal homeostasis, sensing nutrient status to regulate organismal growth and metabolism. We identify here the Drosophila B' regulatory subunit of PP2A (PP2A-B') as a novel, conserved component of the insulin pathway that specifically targets the PP2A holoenzyme to dephosphorylate S6K. PP2A-B' knockout flies have elevated S6K phosphorylation and exhibit phenotypes typical of elevated insulin signaling such as reduced total body triglycerides and reduced longevity. We show that PP2A-B' interacts with S6K both physically and genetically. The human homolog of PP2A-B', PPP2R5C, also counteracts S6K1 phosphorylation, indicating a conserved mechanism in mammals. Since S6K affects development of cancer and metabolic disease, our data identify PPP2R5C as a novel factor of potential medical relevance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / metabolism
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Gene Knockout Techniques
  • Humans
  • Insulin / metabolism
  • Longevity
  • Phosphoprotein Phosphatases / deficiency
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Protein Phosphatase 2 / metabolism*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction
  • Triglycerides / metabolism


  • Drosophila Proteins
  • Insulin
  • Triglycerides
  • Ribosomal Protein S6 Kinases, 70-kDa
  • ribosomal protein S6 kinase, 70kD, polypeptide 1
  • PPP2R5C protein, human
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • tws protein, Drosophila