2uzs: Difference between revisions

==Overview==

Although AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is, a central member of possibly the most frequently activated proliferation, and survival pathway in cancer, mutation of AKT1 has not been widely, reported. Here we report the identification of a somatic mutation in human, breast, colorectal and ovarian cancers that results in a glutamic acid to, lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of, AKT1. Lys 17 alters the electrostatic interactions of the pocket and forms, new hydrogen bonds with a phosphoinositide ligand. This mutation activates, AKT1 by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia, in mice. This mechanism indicates a direct role of AKT1 in human cancer, and adds to the known genetic alterations that promote oncogenesis through, the phosphatidylinositol-3-OH kinase/AKT pathway. Furthermore, the E17K, substitution decreases the sensitivity to an allosteric kinase inhibitor, so this mutation may have important clinical utility for AKT drug, development.

==About this Structure==

[[Category: transport]]