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Akt regulates growth by directly phosphorylating Tsc2.

The direct mechanism by which the serine/threonine kinase Akt (also known as protein kinase B (PKB)) regulates cell growth is unknown. Here, we report that Drosophila melanogaster Akt/PKB stimulates growth by phosphorylating the tuberous sclerosis complex 2 (Tsc2) tumour suppressor and inhibiting formation of a Tsc1-Tsc2 complex. We show that Akt/PKB directly phosphorylates Drosophila Tsc2 in vitro at the conserved residues, Ser 924 and Thr 1518. Mutation of these sites renders Tsc2 insensitive to Akt/PKB signalling, increasing the stability of the Tsc1-Tsc2 complex within the cell. Stimulating Akt/PKB signalling in vivo markedly increases cell growth/size, disrupts the Tsc1-Tsc2 complex and disturbs the distinct subcellular localization of Tsc1 and Tsc2. Furthermore, all Akt/PKB growth signals are blocked by expression of a Tsc2 mutant lacking Akt phosphorylation sites. Thus, Tsc2 seems to be the critical target of Akt in mediating growth signals for the insulin signalling pathway.

Pubmed ID: 12172554


  • Potter CJ
  • Pedraza LG
  • Xu T


Nature cell biology

Publication Data

September 2, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: CA69408

Mesh Terms

  • Animals
  • Binding Sites
  • Cell Division
  • Drosophila Proteins
  • Drosophila melanogaster
  • Eye
  • Humans
  • In Vitro Techniques
  • Insulin
  • Models, Biological
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Repressor Proteins
  • Signal Transduction
  • Subcellular Fractions
  • Tumor Suppressor Proteins