Cited by 5,689Cell death mechanisms and regulationPI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase Signaling

Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery

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Datta, Sandeep Robert, Dudek, Henryk, Tao, Xu, Masters, Shane, Fu, Haian, Gotoh, Yukiko, Greenberg, Michael E·1997·Cell

Abstract

Growth factors can promote cell survival by activating the phosphatidylinositide-3'-OH kinase and its downstream target, the serine-threonine kinase Akt. However, the mechanism by which Akt functions to promote survival is not understood. We show that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates BAD in vitro and in vivo, and blocks the BAD-induced death of primary neurons in a site-specific manner. These findings define a mechanism by which growth factors directly inactivate a critical component of the cell-intrinsic death machinery.

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Authors
Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., & Greenberg, M. E.
Affiliations
  • Boston Children's Hospital (US)
  • Emory University (US)
Corresponding author
Greenberg, Michael E
Venue
Cell
Publisher
Elsevier BV
Published
1997-10
Volume
91
Issue
2
Pages
231-241
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2097767970
Cited by
5,689
References
57
Citations by year
2026: 58 · 2025: 65 · 2024: 70 · 2023: 82 · 2022: 60 · 2021: 88 · 2020: 101 · 2019: 113 · 2018: 110 · 2017: 140 · 2016: 143 · 2015: 163 · 2014: 185 · 2013: 237 · 2012: 242
FWCI
80.36
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (GM 53165)
  • National Institute of Neurological Disorders and Stroke (NS 28829)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
Akt phosphorylation, Bad, Bcl-2 family proteins, PI3K/Akt signaling, apoptosis, cell survival, growth factor signaling, primary neurons, site-specific phosphorylation
MeSH terms
Amino Acid Sequence, Animals, Carrier Proteins, Cell Survival, Insulin-Like Growth Factor I, Mice, Inbred BALB C, Molecular Sequence Data, Neurons, Phosphorylation, Proto-Oncogene Proteins, Serine, Signal Transduction, 3T3 Cells, Cell Death, Protein Serine-Threonine Kinases, bcl-Associated Death Protein, Proto-Oncogene Proteins c-akt, Mice

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