Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations
- Author(s)
- Green, BD; Jabbour, AM; Sandow, JJ; Riffkin, CD; Masouras, D; Daunt, CP; Salmanidis, M; Brumatti, G; Hemmings, BA; Guthridge, MA; Pearson, RB; Ekert, PG;
- Details
- Publication Year 2013-10,Volume 20,Issue #10,Page 1341-1349
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Publication Type
- Journal Article
- 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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- Akt; Bcl-2; interleukin-3; puma
- Research Division(s)
- Cell Signalling And Cell Death
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770321/
- Publisher's Version
- https://doi.org/10.1038/cdd.2013.63
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- © 2013 ADMC Associazione Differenziamento e Morte Cellulare
Creation Date: 2013-10-01 12:00:00