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 journalArticlepeer-review

980 Scopus citations


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
Issue number6
StatePublished - Mar 15 1997
Externally publishedYes


  • CPP32
  • Growth factors
  • Myc
  • cell survival

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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