Cited by 2,551PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer

Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN

Open access
Stambolic, Vuk, Suzuki, Akira, de la Pompa, José Luis, Brothers, Greg M, Mirtsos, Christine, Sasaki, Takehiko, Ruland, Jurgen, Penninger, Josef M +2 more·1998·Cell

Abstract

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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Crossref · 10.1016/s0092-8674(00)81780-8

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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
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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