ArticleCell2018
Akt Kinase Activation Mechanisms Revealed Using Protein Semisynthesis.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
93 citing papers in PubMed, 149 citations in OpenAlex.
- AKT mutant allele-specific activation dictates pharmacologic sensitivities.Nature communications · 2022Trial
- Manganese availability determines insulin sensitivity by enhancing Akt activity.bioRxiv : the preprint server for biology · 2026Article
- T cell receptors equipped with ICOS provide T cells with durable anti-tumor response.Molecular cancer · 2026Article
- Review
- Revealing and Exploiting the Biochemistry ofBiochemistry · 2026Review
- Quercetin Inhibits AKT Ser473 Phosphorylation and Disrupts AKT-Androgen Receptor Signaling in Castration-Resistant Prostate Cancer Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Structural basis for the recruitment and selective phosphorylation of Akt by mTORC2.Science (New York, N.Y.) · 2026Article
- Structural and mechanistic basis of mTORC2 activation of protein kinase AKT/PKB.The Biochemical journal · 2026Review
- A new functional assay reveals that membrane binding is critical for overactivation of the phosphoinositide 3-kinase H1047R mutant.The Journal of biological chemistry · 2026Article
- T-cadherin, a major adiponectin binding partner, suppresses ERK signaling in metabolic tissues.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Characterization of rutin bindingto HRAS and MAPK3 and its clinical prognostic relevancein lung cancer: Using in silico and clinical prognostic experimental design.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- 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
- Transcriptomic analysis and experimental verification reveal the involvement of PI3K/AKT signaling pathway in high-altitude cognitive dysfunction.Frontiers in physiology · 2026Article
- Structural insights of AKT and its activation mechanism for drug development.Molecular diversity · 2025Review
- Distinct Allosteric Networks in CDK4 and CDK6 in the Cell Cycle and in Drug Resistance.Journal of molecular biology · 2025Article
- Novel furo[2,3-RSC medicinal chemistry · 2025Article
- Nanodisc single-molecule pulldown to study lipid-protein interactions.Journal of lipid research · 2025Article
- Allosteric coupling activation mechanism in histidine kinases.Scientific reports · 2025Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Akt is a critical protein kinase that drives cancer proliferation, modulates metabolism, and is activated by C-terminal phosphorylation. The current structural model for Akt activation by C-terminal phosphorylation has centered on intramolecular interactions between the C-terminal tail and the N lobe of the kinase domain. Here, we employ expressed protein ligation to produce site-specifically phosphorylated forms of purified Akt1 that are well suited for mechanistic analysis. Using biochemical, crystallographic, and cellular approaches, we determine that pSer473-Akt activation is driven by an intramolecular interaction between the C-tail and the pleckstrin homology (PH)-kinase domain linker that relieves PH domain-mediated Akt1 autoinhibition. Moreover, dual phosphorylation at Ser477/Thr479 activates Akt1 through a different allosteric mechanism via an apparent activation loop interaction that reduces autoinhibition by the PH domain and weakens PIP3 affinity. These results provide a new framework for understanding how Akt is controlled in cell signaling and suggest distinct functions for differentially modified Akt forms.
Indexed as
Identifiers
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.