Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations
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
WEHI Research Division(s)
Cell Signalling And Cell Death
Rights Notice
© 2013 ADMC Associazione Differenziamento e Morte Cellulare


Creation Date: 2013-10-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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