title: A new mutational AKTivation in the PI3K pathway.
abstract: 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.
authors: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors: Joan
authors: J
authors: Brugge
authors: Mien-Chie
authors: MC
authors: Hung
authors: Gordon B
authors: GB
authors: Mills
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt