Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations

Benjamin D Green, Anissa M Jabbour, Jarrod J Sandow, Christopher D Riffkin, D Masouras, Carmel Patricia Daunt, Marika Salmanidis, Gabriela Brumatti, Brian Hemmings, Mark Andrew Guthridge, Richard Bruce Pearson, Paul G Ekert

Research output: Contribution to journalArticleResearchpeer-review

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. ? 2013 Macmillan Publishers Limited All rights reserved.
Original languageEnglish
Pages (from-to)1341 - 1349
Number of pages9
JournalCell Death and Differentiation
Volume20
Issue number10
DOIs
Publication statusPublished - 2013

Cite this

Green, B. D., Jabbour, A. M., Sandow, J. J., Riffkin, C. D., Masouras, D., Daunt, C. P., ... Ekert, P. G. (2013). Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations. Cell Death and Differentiation, 20(10), 1341 - 1349. https://doi.org/10.1038/cdd.2013.63
Green, Benjamin D ; Jabbour, Anissa M ; Sandow, Jarrod J ; Riffkin, Christopher D ; Masouras, D ; Daunt, Carmel Patricia ; Salmanidis, Marika ; Brumatti, Gabriela ; Hemmings, Brian ; Guthridge, Mark Andrew ; Pearson, Richard Bruce ; Ekert, Paul G. / Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations. In: Cell Death and Differentiation. 2013 ; Vol. 20, No. 10. pp. 1341 - 1349.
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title = "Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations",
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. ? 2013 Macmillan Publishers Limited All rights reserved.",
author = "Green, {Benjamin D} and Jabbour, {Anissa M} and Sandow, {Jarrod J} and Riffkin, {Christopher D} and D Masouras and Daunt, {Carmel Patricia} and Marika Salmanidis and Gabriela Brumatti and Brian Hemmings and Guthridge, {Mark Andrew} and Pearson, {Richard Bruce} and Ekert, {Paul G}",
year = "2013",
doi = "10.1038/cdd.2013.63",
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Green, BD, Jabbour, AM, Sandow, JJ, Riffkin, CD, Masouras, D, Daunt, CP, Salmanidis, M, Brumatti, G, Hemmings, B, Guthridge, MA, Pearson, RB & Ekert, PG 2013, 'Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations' Cell Death and Differentiation, vol. 20, no. 10, pp. 1341 - 1349. https://doi.org/10.1038/cdd.2013.63

Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations. / Green, Benjamin D; Jabbour, Anissa M; Sandow, Jarrod J; Riffkin, Christopher D; Masouras, D; Daunt, Carmel Patricia; Salmanidis, Marika; Brumatti, Gabriela; Hemmings, Brian; Guthridge, Mark Andrew; Pearson, Richard Bruce; Ekert, Paul G.

In: Cell Death and Differentiation, Vol. 20, No. 10, 2013, p. 1341 - 1349.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Green, Benjamin D

AU - Jabbour, Anissa M

AU - Sandow, Jarrod J

AU - Riffkin, Christopher D

AU - Masouras, D

AU - Daunt, Carmel Patricia

AU - Salmanidis, Marika

AU - Brumatti, Gabriela

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AU - Pearson, Richard Bruce

AU - Ekert, Paul G

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AB - 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. ? 2013 Macmillan Publishers Limited All rights reserved.

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