Akt2 Kinase Suppresses Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH)-mediated Apoptosis in Ovarian Cancer Cells via Phosphorylating GAPDH at Threonine 237 and Decreasing Its Nuclear Translocation
Open accessAbstract
Protein kinase B (Akt) plays important roles in regulation of cell growth and survival, but while many aspects of its mechanism of action are known, there are potentially additional regulatory events that remain to be discovered. Here we detected a 36-kDa protein that was co-immunoprecipitated with protein kinase Bβ (Akt2) in OVCAR-3 ovarian cancer cells. The protein was identified to be glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by MALDI-TOF/TOF MS, and the interaction of Akt2 and GAPDH was verified by reverse immunoprecipitation. Our further study showed that Akt2 may suppress GAPDH-mediated apoptosis in ovarian cancer cells. Overexpression of GAPDH increased ovarian cancer cell apoptosis induced by H(2)O(2), which was inhibited by Akt2 overexpression and restored by the PI3K/Akt inhibitor wortmannin or Akt2 siRNA. Akt2 phosphorylated Thr-237 of GAPDH and decreased its nuclear translocation, an essential step for GAPDH-mediated apoptosis. The interaction between Akt2 and GAPDH may be important in ovarian cancer as immunohistochemical analysis of 10 normal and 30 cancerous ovarian tissues revealed that decreased nuclear expression of GAPDH correlated with activation (phosphorylation) of Akt2. In conclusion, our study suggests that activated Akt2 may increase ovarian cancer cell survival via inhibition of GAPDH-induced apoptosis. This effect of Akt2 is partly mediated by its phosphorylation of GAPDH at Thr-237, which results in the inhibition of GAPDH nuclear translocation.
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Phosphorylation of GAPDH occurs through the Src/PI3K/AKT pathway, often downstream of receptor tyrosine kinase activation.
“Phosphorylation of GAPDH occurs through the Src/PI3K/AKT pathway, often downstream of receptor tyrosine kinase activation [76].”
From Gene Expression Analysis of Zebrafish Melanocytes, Iridophores, and Retinal Pigmented Epithelium Reveals Indicators of Biological Function and Developmental Origin (2013) · cites this paper as [76]
The Results (page not provided) show that Akt2 phosphorylates GAPDH and that wortmannin or Akt2 siRNA inhibits the observed phosphorylation; the paper also places Akt downstream of PI3K. The cited passages do not establish a Src/PI3K/Akt route to GAPDH phosphorylation or show that it often follows receptor tyrosine kinase activation. (LLM, conf=0.88)
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- Sahin, O., Löbke, C., Korf, U., Appelhans, H., Sültmann, H., Poustka, A., Wiemann, S., and Arlt, D. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 6579 -6584
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- Authors
- Huang, Q., Lan, F., Zheng, Z., Xie, F., Han, J., Dong, L., Xie, Y., & Zheng, F.
- Affiliations
- Fuzhou General Hospital of Nanjing Military Command (CN)
- Corresponding author
- Huang, Qiaojia
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 286
- Issue
- 49
- Pages
- 42211-42220
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3234938
- OpenAlex
- W2051124098
- Cited by
- 97
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 8 · 2019: 4 · 2018: 10 · 2017: 9 · 2016: 3 · 2015: 9 · 2014: 11 · 2013: 7 · 2012: 7
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Fujian Province
- Fuzhou General Hospital
- 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 › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- AKT2, glyceraldehyde-3-phosphate dehydrogenase, nuclear translocation, apoptosis, ovarian cancer, PI3K/Akt signaling, wortmannin, cell survival
- MeSH terms
- Amino Acid Sequence, Cell Survival, Cytoplasm, Female, Glyceraldehyde-3-Phosphate Dehydrogenases, Humans, Models, Molecular, Molecular Sequence Data, Ovarian Neoplasms, Phosphorylation, Mutagenesis, Site-Directed, Apoptosis, Active Transport, Cell Nucleus, RNA Interference, Cell Line, Tumor, Proto-Oncogene Proteins c-akt
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