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- Title
Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations.
- Authors
Green, B D; Jabbour, A M; Sandow, J J; Riffkin, C D; Masouras, D; Daunt, C P; Salmanidis, M; Brumatti, G; Hemmings, B A; Guthridge, M A; Pearson, R B; Ekert, P G
- Abstract
The activation of the Akt signalling in response to cytokine receptor signalling promotes protein synthesis, cellular growth and proliferation. To determine the role of Akt in interleukin-3 (IL-3) signalling, we generated IL-3-dependent myeloid cell lines from mice lacking Akt1, Akt2 or Akt3. Akt1 deletion resulted in accelerated apoptosis at low concentrations of IL-3. Expression of constitutively active Akt1 was sufficient to delay apoptosis in response to IL-3 withdrawal, but not sufficient to induce proliferation in the absence of IL-3. Akt1 prolonged survival of Bim- or Bad-deficient cells, but not cells lacking Puma, indicating that Akt1-dependent repression of apoptosis was in part dependent on Puma and independent of Bim or Bad. Our data show that a key role of Akt1 during IL-3 signalling is to repress p53-dependent apoptosis pathways, including transcriptional upregulation of Puma. Moreover, our data indicate that regulation of BH3-only proteins by Akt is dispensable for Akt-dependent cell survival.
- Subjects
APOPTOSIS; CYTOKINE receptors; CYTOKINES; PROTEIN synthesis; CELL growth; CELL proliferation
- Publication
Cell Death & Differentiation, 2013, Vol 20, Issue 10, p1341
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/cdd.2013.63