A new mutational AKTivation in the PI3K pathway

Cancer Cell. 2007 Aug;12(2):104-7. doi: 10.1016/j.ccr.2007.07.014.


Although multiple members of the phosphatidylinositol-3-kinase pathway (PI3K) are targeted by germline or somatic mutations, functional mutations in the three akt isoforms have proven elusive. This is somewhat surprising, as AKT represents a key node in the PI3K pathway, exhibiting transforming activity when incorporated into the AKT8 retrovirus. A recent report in Nature identifies a transforming E17K PH domain mutation in akt1 in breast (8%), colorectal (6%), and ovarian (2%) cancers. E17K-akt1 transforming activity appears due to PtdIns(3,4)P2- and PtdIns(3,4,5)P3-independent recruitment of AKT1 to the membrane. This novel observation raises important theoretical and clinical questions.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation / physiology*
  • Humans
  • Mutation / genetics*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics*
  • Signal Transduction*


  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt