ArticleeLife2020
The structural determinants of PH domain-mediated regulation of Akt revealed by segmental labeling.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- The multifaceted significance of phosphoinositides in endocytic trafficking.FEBS letters · 2026Review
- Structural and mechanistic basis of mTORC2 activation of protein kinase AKT/PKB.The Biochemical journal · 2026Review
- Review
- The UFL1-AKT positive feedback loop promotes breast cancer progression by enhancing lipid synthesis.Nature communications · 2026Article
- The structural heterogeneity of AKT autoinhibition.Protein science : a publication of the Protein Society · 2026Article
- Selective phosphoinositide 3-kinase inhibitors and implication in diabetic retinopathy as pharmacological tools.Frontiers in pharmacology · 2026Review
- Structural insights of AKT and its activation mechanism for drug development.Molecular diversity · 2025Review
- Investigation of Akt1 behavior on gold surface from molecular dynamics insight.Scientific reports · 2025Article
- Endometrial cancer: from clinical reality to molecular treatment.Discover oncology · 2025Review
- AGC family kinase of Entamoeba histolytica: Decoding the members biochemically.PLoS pathogens · 2024Article
- Capturing Autoinhibited PDK1 Reveals the Linker's Regulatory Role, Informing Innovative Inhibitor Design.Journal of chemical information and modeling · 2024Article
- Reused Protein Segments Linked to Functional Dynamics.Molecular biology and evolution · 2024Article
- Akt is a mediator of artery specification during zebrafish development.Development (Cambridge, England) · 2024Article
- CDK2 and CDK4: Cell Cycle Functions Evolve Distinct, Catalysis-Competent Conformations, Offering Drug Targets.JACS Au · 2024Article
- Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease.Scientific reports · 2024Article
- The cryo-EM structure of ASK1 reveals an asymmetric architecture allosterically modulated by TRX1.eLife · 2024Article
- AKT1 interacts with DHX9 to Mitigate R Loop-Induced Replication Stress in Ovarian Cancer.Cancer research · 2024Article
- Selectivity Studies and Free Energy Calculations of AKT Inhibitors.Molecules (Basel, Switzerland) · 2024Article
- A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway.Molecular cancer · 2024Article
- Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt.Cellular and molecular life sciences : CMLS · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Akt is a critical protein kinase that governs cancer cell growth and metabolism. Akt appears to be autoinhibited by an intramolecular interaction between its N-terminal pleckstrin homology (PH) domain and kinase domain, which is relieved by C-tail phosphorylation, but the precise molecular mechanisms remain elusive. Here, we use a combination of protein semisynthesis, NMR, and enzymological analysis to characterize structural features of the PH domain in its autoinhibited and activated states. We find that Akt autoinhibition depends on the length/flexibility of the PH-kinase linker. We identify a role for a dynamic short segment in the PH domain that appears to regulate autoinhibition and PDK1-catalyzed phosphorylation of Thr308 in the activation loop. We determine that Akt allosteric inhibitor MK2206 drives distinct PH domain structural changes compared to baseline autoinhibited Akt. These results highlight how the conformational plasticity of Akt governs the delicate control of its catalytic properties.
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What OpenQuestion holds
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.