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Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery
Open accessAbstract
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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“which is a critical mediator of neuronal survival (Datta et al., 1997; Dudek et al., 1997).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Datta et al., 1997
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Metadata
- 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
- bronze
- doi.org
- Licence
- 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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