The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal
- PMID: 9087425
- DOI: 10.1101/gad.11.6.701
The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal
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.
Similar articles
-
PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond.Trends Biochem Sci. 1997 Sep;22(9):355-8. doi: 10.1016/s0968-0004(97)01097-9. Trends Biochem Sci. 1997. PMID: 9301337 Review.
-
Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf-1/mitogen-activated protein kinase pathway activation.Mol Cell Biol. 1997 Aug;17(8):4406-18. doi: 10.1128/MCB.17.8.4406. Mol Cell Biol. 1997. PMID: 9234699 Free PMC article.
-
Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway.EMBO J. 1997 May 15;16(10):2783-93. doi: 10.1093/emboj/16.10.2783. EMBO J. 1997. PMID: 9184223 Free PMC article.
-
Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB.Nature. 1997 Feb 6;385(6616):544-8. doi: 10.1038/385544a0. Nature. 1997. PMID: 9020362
-
A target for phosphoinositide 3-kinase: Akt/PKB.Trends Biochem Sci. 1995 Nov;20(11):441-2. doi: 10.1016/s0968-0004(00)89097-0. Trends Biochem Sci. 1995. PMID: 8578585 Review. No abstract available.
Cited by
-
Deguelin Restores Paclitaxel Sensitivity in Paclitaxel-Resistant Ovarian Cancer Cells via Inhibition of the EGFR Signaling Pathway.Cancer Manag Res. 2024 May 28;16:507-525. doi: 10.2147/CMAR.S457221. eCollection 2024. Cancer Manag Res. 2024. PMID: 38827785 Free PMC article.
-
Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins.Int J Mol Sci. 2023 Dec 25;25(1):323. doi: 10.3390/ijms25010323. Int J Mol Sci. 2023. PMID: 38203494 Free PMC article. Review.
-
Endoxifen downregulates AKT phosphorylation through protein kinase C beta 1 inhibition in ERα+ breast cancer.NPJ Breast Cancer. 2023 Dec 19;9(1):101. doi: 10.1038/s41523-023-00606-2. NPJ Breast Cancer. 2023. PMID: 38114522 Free PMC article.
-
Changes in the Acetylcholinesterase Enzymatic Activity in Tumor Development and Progression.Cancers (Basel). 2023 Sep 19;15(18):4629. doi: 10.3390/cancers15184629. Cancers (Basel). 2023. PMID: 37760598 Free PMC article. Review.
-
Culturing characteristics of Hanwoo myosatellite cells and C2C12 cells incubated at 37°C and 39°C for cultured meat.J Anim Sci Technol. 2023 May;65(3):664-678. doi: 10.5187/jast.2023.e10. Epub 2023 May 31. J Anim Sci Technol. 2023. PMID: 37332290 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous