Genetic analysis of protein kinase B (AKT) in Drosophila

Brian E. Staveley, Laurent Ruel, Jing Jin, Vuk Stambolic, Fabrizio G. Mastronardi, Pascal Heitzler, James R. Woodgett, Armen S. Manoukian*

*Corresponding author for this work

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

The decision between survival and death is an important aspect of cellular regulation during development and malignancy. Central to this regulation is the process of apoptosis, which is conserved in multicellular organisms [1]. A variety of signalling cascades have been implicated in modulation of apoptosis, including the phosphatidylinositol (PI) 3-kinase pathway. Activation of PI 3-kinase is protective, and inhibition 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 been linked to its activation of the pleckstrin homology (PH)-domain-containing protein kinase B (PKB or AKT) [8]. PKB/AKT was identified from an oncogene, v-akt, found in a rodent T-cell lymphoma [9]. To initiate a genetic analysis of PKB, we have isolated and characterized a Drosophila 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 implicate Dakt1 as a cell survival gene in Drosophila, consistent with cell protection studies in mammals.

Original languageEnglish (US)
Pages (from-to)599-603
Number of pages5
JournalCurrent Biology
Volume8
Issue number10
StatePublished - May 7 1998

Fingerprint

Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinase
protein kinases
Drosophila
genetic techniques and protocols
phosphatidylinositol 3-kinase
apoptosis
Apoptosis
Chemical activation
Anoikis
pleckstrin
hides and skins
neurotrophins
Mammals
Cytoprotection
T-cells
T-Cell Lymphoma
Macrophages
oncogenes
caspases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Staveley, B. E., Ruel, L., Jin, J., Stambolic, V., Mastronardi, F. G., Heitzler, P., ... Manoukian, A. S. (1998). Genetic analysis of protein kinase B (AKT) in Drosophila. Current Biology, 8(10), 599-603.
Staveley, Brian E. ; Ruel, Laurent ; Jin, Jing ; Stambolic, Vuk ; Mastronardi, Fabrizio G. ; Heitzler, Pascal ; Woodgett, James R. ; Manoukian, Armen S. / Genetic analysis of protein kinase B (AKT) in Drosophila. In: Current Biology. 1998 ; Vol. 8, No. 10. pp. 599-603.
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Staveley, BE, Ruel, L, Jin, J, Stambolic, V, Mastronardi, FG, Heitzler, P, Woodgett, JR & Manoukian, AS 1998, 'Genetic analysis of protein kinase B (AKT) in Drosophila', Current Biology, vol. 8, no. 10, pp. 599-603.

Genetic analysis of protein kinase B (AKT) in Drosophila. / Staveley, Brian E.; Ruel, Laurent; Jin, Jing; Stambolic, Vuk; Mastronardi, Fabrizio G.; Heitzler, Pascal; Woodgett, James R.; Manoukian, Armen S.

In: Current Biology, Vol. 8, No. 10, 07.05.1998, p. 599-603.

Research output: Contribution to journalArticle

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Staveley BE, Ruel L, Jin J, Stambolic V, Mastronardi FG, Heitzler P et al. Genetic analysis of protein kinase B (AKT) in Drosophila. Current Biology. 1998 May 7;8(10):599-603.