The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal.
10.1101/gad.11.6.701
Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
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.

Bibliography

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 & Development, 11(6), 701–713.

Authors 7
  1. S G Kennedy (first)
  2. A J Wagner (additional)
  3. S D Conzen (additional)
  4. J Jordán (additional)
  5. A Bellacosa (additional)
  6. P N Tsichlis (additional)
  7. N Hay (additional)
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Dates
Type When
Created 18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited 3 years, 9 months ago (Nov. 14, 2021, 10 p.m.)
Indexed 3 weeks, 1 day ago (Aug. 7, 2025, 4:56 a.m.)
Issued 28 years, 5 months ago (March 15, 1997)
Published 28 years, 5 months ago (March 15, 1997)
Published Online 28 years, 5 months ago (March 15, 1997)
Published Print 28 years, 5 months ago (March 15, 1997)
Funders 0

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@article{Kennedy_1997, title={The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal.}, volume={11}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.11.6.701}, DOI={10.1101/gad.11.6.701}, number={6}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Kennedy, S G and Wagner, A J and Conzen, S D and Jordán, J and Bellacosa, A and Tsichlis, P N and Hay, N}, year={1997}, month=mar, pages={701–713} }