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

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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

DOI 10.1016/s0092-8674(00)80405-5

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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
ORCID: Datta, Sandeep Robert
Fu, Haian
Gotoh, Yukiko
Greenberg, Michael E
Venue: Cell
Publisher: Elsevier BV
Published: 1997-10
Volume: 91
Issue: 2
Pages: 231-241
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(00)80405-5
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: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5768 d)
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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Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery

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