guthridge-akt1isthe-2013.pdf (575.83 kB)
Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations
journal contribution
posted on 2013-01-01, 00:00 authored by B D Green, A M Jabbour, J J Sandow, C D Riffkin, D Masouras, C P Daunt, M Salmanidis, G Brumatti, B A Hemmings, Mark GuthridgeMark Guthridge, R B Pearson, P G EkertThe 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.
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Journal
Cell death & differentiationVolume
20Issue
10Pagination
1341 - 1349Publisher
SpringerLocation
Cham, SwitzerlandPublisher DOI
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ISSN
1350-9047eISSN
1476-5403Language
engPublication classification
C1.1 Refereed article in a scholarly journalUsage metrics
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