ArticleACS chemical biology2022
Multifaceted Regulation of Akt by Diverse C-Terminal Post-translational Modifications.
Article in ACS chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Allosteric activation of RNF20/RNF40-RAD6A-mediated H2BK120 monoubiquitylation by H2BS112 GlcNAcylation.Nature chemical biology · 2026Article
- Revealing and Exploiting the Biochemistry ofBiochemistry · 2026Review
- Structural basis for the recruitment and selective phosphorylation of Akt by mTORC2.Science (New York, N.Y.) · 2026Article
- Review
- The structural heterogeneity of AKT autoinhibition.Protein science : a publication of the Protein Society · 2026Article
- Engineered reactivity of a bacterial E1-like enzyme enables ATP-driven modification of protein and peptide C termini.Nature chemistry · 2025Article
- Advances in the chemical synthesis of human proteoforms.Science China. Life sciences · 2025Review
- Metabolic Side Effects from Antipsychotic Treatment with Clozapine Linked to Aryl Hydrocarbon Receptor (AhR) Activation.Biomedicines · 2024Review
- The post-translational modification O-GlcNAc is a sensor and regulator of metabolism.Open biology · 2024Review
- Article
- Engineered reactivity of a bacterial E1-like enzyme enables ATP-driven modification of protein C termini.bioRxiv : the preprint server for biology · 2024Article
- Inhibiting MEK1 R189 citrullination enhances the chemosensitivity of docetaxel to multiple tumour cells.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Review
- NEDD4L in human tumors: regulatory mechanisms and dual effects on anti-tumor and pro-tumor.Frontiers in pharmacology · 2023Review
- Revving the engine: PKB/AKT as a key regulator of cellular glucose metabolism.Frontiers in physiology · 2023Review
- Analyzing protein posttranslational modifications using enzyme-catalyzed expressed protein ligation.Methods in enzymology · 2023Article
- Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Akt is a Ser/Thr protein kinase that regulates cell growth and metabolism and is considered a therapeutic target for cancer. Regulation of Akt by membrane recruitment and post-translational modifications (PTMs) has been extensively studied. The most well-established mechanism for cellular Akt activation involves phosphorylation on its activation loop on Thr308 by PDK1 and on its C-terminal tail on Ser473 by mTORC2. In addition, dual phosphorylation on Ser477 and Thr479 has been shown to activate Akt. Other C-terminal tail PTMs have been identified, but their functional impacts have not been well-characterized. Here, we investigate the regulatory effects of phosphorylation of Tyr474 and O-GlcNAcylation of Ser473 on Akt. We use expressed protein ligation as a tool to produce semisynthetic Akt proteins containing phosphoTyr474 and O-GlcNAcSer473 to dissect the enzymatic functions of these PTMs. We find that O-GlcNAcylation at Ser473 and phosphorylation at Tyr474 can also partially increase Akt's kinase activity toward both peptide and protein substrates. Additionally, we performed kinase assays employing human protein microarrays to investigate global substrate specificity of Akt, comparing phosphorylated versus O-GlcNAcylated Ser473 forms. We observed a high similarity in the protein substrates phosphorylated by phosphoSer473 Akt and O-GlcNAcSer473 Akt. Two Akt substrates identified using microarrays, PPM1H, a protein phosphatase, and NEDD4L, an E3 ubiquitin ligase, were validated in solution-phase assays and cell transfection experiments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.