Phosphorylation of Akt at the C-terminal tail triggers Akt Activation
Open accessAbstract
Aberrant hyper-activation of the protein kinase Akt plays a critical role in promoting tumorigenesis. Mechanistically, previous studies establish that phosphorylation of Akt at S473 and T308 by mTORC2 and PDK1, respectively, is necessary for its full activation, thereby having been used as Akt activation markers. Recently, we report that phosphorylation of S477 and T479 at the extreme C-terminus of Akt1 promotes Akt1 activation. We further demonstrate that Akt1 pS477 and pT479 events are governed by Cdk2/Cyclin A or mTORC2 under distinct cellular contexts such as cell cycle progression or growth stimulation conditions. Here, we summarize our major findings regarding the biological significance for pS477/pT479-mediated activation of Akt and also provide perspectives for future follow-up studies.
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Through these molecular mechanisms, GLP-1 plays a crucial role in the treatment of diabetes by enhancing the function and protecting pancreatic β-cells from apoptosis, and it may also offer potential therapeutic benefits in cardiovascular and neural protection.
“Through these molecular mechanisms, GLP-1 not only plays a crucial role in the treatment of diabetes by enhancing the function and protecting pancreatic β-cells from apoptosis, but it may also offer potential therapeutic benefits in fields such as cardiovascular and neural protection.198,205,206”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [198]
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- Authors
- Liu, P., Wang, Z., & Wei, W.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Soochow University (CN)
- Corresponding author
- Wei, Wenyi
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2014-06-16
- Volume
- 13
- Issue
- 14
- Pages
- 2162-2164
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC4111671
- OpenAlex
- W2085555658
- Cited by
- 49
- References
- 10
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 1
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81172087)
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL007893)
- National Cancer Institute (R01CA177910, CA177910)
- National Institute of General Medical Sciences (GM094777, GM-089763, R01GM094777, R01GM089763)
- 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
- AKT1, Akt phosphorylation, C-terminal tail, Akt activation, mTORC2, CDK2/cyclin A, cell cycle progression, carcinogenesis, PDK1
- MeSH terms
- Mechanistic Target of Rapamycin Complex 2, Animals, Cell Transformation, Neoplastic, Enzyme Activation, Humans, Neoplasms, Phosphorylation, Protein Kinase C, Signal Transduction, Protein Structure, Tertiary, Cell Cycle Proteins, Multiprotein Complexes, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases
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