Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
Open accessAbstract
PTEN is a tumor suppressor with sequence homology to protein tyrosine phosphatases and the cytoskeletal protein tensin. mPTEN-mutant mouse embryos display regions of increased proliferation. In contrast, mPTEN-deficient immortalized mouse embryonic fibroblasts exhibit decreased sensitivity to cell death in response to a number of apoptotic stimuli, accompanied by constitutively elevated activity and phosphorylation of protein kinase B/Akt, a crucial regulator of cell survival. Expression of exogenous PTEN in mutant cells restores both their sensitivity to agonist-induced apoptosis and normal pattern of PKB/Akt phosphorylation. Furthermore, PTEN negatively regulates intracellular levels of phosphatidylinositol (3,4,5) trisphosphate in cells and dephosphorylates it in vitro. Our results show that PTEN may exert its role as a tumor suppressor by negatively regulating the PI3'K/PKB/Akt signaling pathway.
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PTEN antagonizes AKT activity.
“This protein antagonizes the activity of the serine-threonine kinase AKT (Stambolic et al., 1998), 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 Stambolic et al., 1998
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- Authors
- Stambolic, V., Suzuki, A., de la Pompa, J. L., Brothers, G. M., Mirtsos, C., Sasaki, T., Ruland, J., Penninger, J. M., Siderovski, D. P., & Mak, T. W.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Mak, Tak W
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 95
- Issue
- 1
- Pages
- 29-39
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1998038367
- Cited by
- 2,551
- References
- 59
- Citations by year
- 2026: 27 · 2025: 37 · 2024: 65 · 2023: 65 · 2022: 48 · 2021: 77 · 2020: 85 · 2019: 96 · 2018: 91 · 2017: 89 · 2016: 84 · 2015: 87 · 2014: 107 · 2013: 120 · 2012: 117
- FWCI
- 35.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- PTEN, tumor suppressor, Akt/protein kinase B, cell survival, apoptosis, PI3K/Akt signaling, phosphatidylinositol 3,4,5-trisphosphate, protein tyrosine phosphatase, tensin
- MeSH terms
- Animals, Cell Division, Cell Survival, Cells, Cultured, Female, Fibroblasts, Phosphoric Monoester Hydrolases, Proto-Oncogene Proteins, Substrate Specificity, Genes, Tumor Suppressor, Mutagenesis, Protein Tyrosine Phosphatases, Apoptosis, Protein Serine-Threonine Kinases, Phosphatidylinositol Phosphates, Tumor Suppressor Proteins, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Mice
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