Cited by 2,436PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingFOXO transcription factor regulation

Regulation of neuronal survival by the serine-threonine protein kinase Akt

Dudek, Henryk, Datta, Sandeep Robert, Franke, Thomas F., Birnbaum, Morris J., Yao, Ryoji, Cooper, Geoffrey M., Segal, Rosalind A., Kaplan, David R. +1 more·1997·Science

Abstract

A signaling pathway was delineated by which insulin-like growth factor 1 (IGF-1) promotes the survival of cerebellar neurons. IGF-1 activation of phosphoinositide 3-kinase (PI3-K) triggered the activation of two protein kinases, the serine-threonine kinase Akt and the p70 ribosomal protein S6 kinase (p70(S6K)). Experiments with pharmacological inhibitors, as well as expression of wild-type and dominant-inhibitory forms of Akt, demonstrated that Akt but not p70(S6K) mediates PI3-K-dependent survival. These findings suggest that in the developing nervous system, Akt is a critical mediator of growth factor-induced neuronal survival.

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Crossref · 10.1126/science.275.5300.661

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Authors
Dudek, H., Datta, S. R., Franke, T. F., Birnbaum, M. J., Yao, R., Cooper, G. M., Segal, R. A., Kaplan, D. R., & Greenberg, M. E.
Affiliations
  • Harvard University (US)
  • Montreal Neurological Institute and Hospital (CA)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Datta, Sandeep Robert
  • Franke, Thomas F.
  • Greenberg, Michael E.
Venue
Science
Published
1997-01-31
Volume
275
Issue
5300
Pages
661-665
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2048121649
Cited by
2,436
References
38
Citations by year
2026: 13 · 2025: 22 · 2024: 15 · 2023: 27 · 2022: 27 · 2021: 23 · 2020: 29 · 2019: 47 · 2018: 42 · 2017: 50 · 2016: 51 · 2015: 62 · 2014: 76 · 2013: 87 · 2012: 61
FWCI
66.02
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ca043855-12, 7r01dk039519-08)
  • National Cancer Institute (R01CA018689, R01 CA 43855, R01 CA 18689)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK39519)
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 › FOXO transcription factor regulation
Keywords
Akt, neuronal survival, insulin-like growth factor I, phosphatidylinositol 3-kinase, cerebellar neurons, growth factor signaling, dominant-negative Akt, neuroprotection
MeSH terms
Wortmannin, Androstadienes, Animals, Cell Survival, Cells, Cultured, Cerebellum, Chromones, Enzyme Activation, Enzyme Inhibitors, Insulin, Insulin-Like Growth Factor I, Morpholines, Neurons, Proto-Oncogene Proteins, Transfection, Signal Transduction, Apoptosis, Protein Serine-Threonine Kinases, Phosphotransferases (Alcohol Group Acceptor), Calcium-Calmodulin-Dependent Protein Kinases, Phosphatidylinositol 3-Kinases, Ribosomal Protein S6 Kinases, Proto-Oncogene Proteins c-akt, Rats

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