PIKKing on PKB: regulation of PKB activity by phosphorylation

Curr Opin Cell Biol. 2009 Apr;21(2):256-61. doi: 10.1016/j.ceb.2009.02.002. Epub 2009 Mar 19.


Ser/Thr protein kinase PKB/Akt is a key regulator of a wide range of cellular processes including growth, proliferation and survival. PKB is clearly a crucial signaling molecule and extensive research efforts aim to understand its regulation and action. Recent studies of the regulation of PKB activity by hydrophobic motif phosphorylation have yielded several exciting findings about members of the PI3-kinase-like family of kinases (PIKKs) acting as PKB regulators. Mammalian target of rapamycin complex 2 (mTORC2) and DNA-dependent protein kinase (DNA-PK) can both phosphorylate Ser473 and activate PKB. This present review concerns PKB regulation by mTORC2 and DNA-PK in a stimulus-dependent and context-dependent manner and the possible implications of this for PKB activity, substrate specificity and therapeutic intervention.

Publication types

  • Review

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • DNA-Activated Protein Kinase / metabolism*
  • Enzyme Activation
  • Humans
  • Neoplasms / therapy
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / physiology
  • Transcription Factors / metabolism*


  • CRTC2 protein, human
  • Transcription Factors
  • 3-Phosphoinositide-Dependent Protein Kinases
  • DNA-Activated Protein Kinase
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt