The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal

Scott G. Kennedy, Andrew J. Wagner, Suzanne D. Conzen, Joaquín Jordán, Alfonso Bellacosa, Philip N. Tsichlis, Nissim Hay

Research output: Contribution to journalArticle

945 Scopus citations

Abstract

Serum and certain growth factors have the ability to inhibit programmed cell death (apoptosis) and promote survival. The mechanism by which growth factors deliver an anti-apoptotic signal and the mechanism by which this survival signal is uncoupled from mitogenesis are not clear. We studied five downstream effectors of growth factor receptors-Ras, Raf, Src, phosphoinositide 3-kinase (PI 3-kinase), and Akt (PKB)for their abilities to block apoptosis. Activated forms of Ras, Raf, and Src, although transforming, were not sufficient to deliver a survival signal upon serum withdrawal. In contrast, inhibition of PI 3-kinase accelerated apoptosis, and an activated form of the serine/threonine kinase Akt, a downstream effector of PI 3- kinase, blocked apoptosis. The ability of Akt to promote survival was dependent on and proportional to its kinase activity. In Rat1a fibroblasts, activated Akt did not alter Bcl-2 or Bcl-X(L) expression but inhibited Ced3/ICE-like activity. Thus, the PI 3-kinase/Akt (PKB) signaling pathway transduces a survival signal that ultimately blocks Ced3/ICE-like activity. These results suggest that uncoupling of survival and mitogenesis can be explained by differing abilities of distinct mitogens to efficiently induce the PI 3-kinase/Akt signaling pathway.

Original languageEnglish (US)
Pages (from-to)701-713
Number of pages13
JournalGenes and Development
Volume11
Issue number6
DOIs
StatePublished - Mar 15 1997
Externally publishedYes

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Keywords

  • cell survival
  • CPP32
  • Growth factors
  • Myc

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Kennedy, S. G., Wagner, A. J., Conzen, S. D., Jordán, J., Bellacosa, A., Tsichlis, P. N., & Hay, N. (1997). The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes and Development, 11(6), 701-713. https://doi.org/10.1101/gad.11.6.701