GENETIC-ANALYSIS OF PROTEIN-KINASE-B (AKT) IN DROSOPHILA

The decision between survival and death is an important aspect of cell ular regulation during development and malignancy. Central to this reg ulation is the process of apoptosis, which is conserved in multicellul ar organisms [1], A variety of signalling cascades have been implicate d in modulation of apoptosis, including the phosphatidylinositol (PI) 3-kinase pathway. Activation of PI 3-kinase is protective, and inhibit ion of this lipid kinase enhances cell death under several conditions including deregulated expression of c-Myc, neurotrophin withdrawal and anoikis [2-7], Recently, the protective effects of PI 3-kinase have b een linked to its activation of the pleckstrin homology (PH)-domain-co ntaining protein kinase a (PKB or AKT) [8]. PKB/AKT was identified fro m an oncogene, v-akt, found in a rodent T-cell lymphoma [9], To initia te a genetic analysis of PKB, we have isolated and characterized a Dro sophila PKB/AKT mutant (termed Dakt1) that exhibits ectopic apoptosis during embryogenesis as judged by induction of membrane blebbing, DNA fragmentation and macrophage infiltration. Apoptosis caused by loss of Dakt function is rescued by caspase suppression but is distinct from the previously described reaper/grim/hid functions. these data implica te Dakt1 as a cell survival gene in Drosophila, consistent with cell p rotection studies in mammals. (C) Current Biology Ltd ISSN 0960-9822.