ArticleeLife2021
Akt phosphorylates insulin receptor substrate to limit PI3K-mediated PIP3 synthesis.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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Who cites it
50 citing papers in PubMed, 77 citations in OpenAlex.
- Article
- Chronic low-dose of BPS and PFOS alter adipogenic programming and impair insulin responsiveness in human adipocytes.Journal of endocrinological investigation · 2026Article
- Material Basis and Mechanisms of Action of PuRenDan in the Treatment of Type 2 Diabetes Mellitus: An Integrated Network Pharmacology and Molecular Simulation Study.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Magnesium as a Bioenergetic Checkpoint Linking Mitochondrial Function, Metabolic Disease, and Aging.Aging cell · 2026Review
- Reprogramming insulin receptor activation with a de novo agonist to overcome severe insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- STEAP2-associated modulation of PI3K/AKT/mTOR signaling contributes to ginkgetin-induced apoptosis in bladder cancer cells.Hereditas · 2026Article
- Structural and mechanistic basis of mTORC2 activation of protein kinase AKT/PKB.The Biochemical journal · 2026Review
- Lipidomic Analysis of Plasma Extracellular Vesicles from Adiponectin Deficient Mice or Metabolic Syndrome Patients Reveals Pro-Oxidative and Pro-Inflammatory Lipid Signatures Correlating with Metabolic Dysfunction.Journal of extracellular vesicles · 2026Article
- Article
- Role of insulin-like growth factor/receptor signaling in hepatocellular carcinoma.Hepatology forum · 2026Review
- Linear Causal Discovery with Interventional Constraints.Machine learning · 2026Article
- Machine learning and bioinformatics identify and validate membrane protein biomarkers for type 2 diabetes mellitus.Frontiers in endocrinology · 2026Article
- Transcriptomic analysis and experimental verification reveal the involvement of PI3K/AKT signaling pathway in high-altitude cognitive dysfunction.Frontiers in physiology · 2026Article
- Chromium as a Modulator of Insulin Receptor Activity: A Systematic Review of Its Role in Metabolic Syndrome and Type 2 Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Pharmacological modulation of the PI3K/AKT/GSK3β axis: a new frontier in Alzheimer's disease treatment.Inflammopharmacology · 2026Review
- Proteomics analysis reveals progesterone receptor induced mitochondria-mediated apoptosis in breast cancer cells.Scientific reports · 2025Article
- PI3 K/AKT/mTOR pathway and its role in breast cancer stem cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting of the PI3 K/AKT/GSK3β Pathway in Parkinson's Disease: A Therapeutic Blueprint.Molecular neurobiology · 2025Review
- Computational Modeling of PI3K/AKT Pathway in Bipolar Disorder and Type 2 Diabetes: Implications for Lithium Treatment and Curcumin as a Potential Alternative.International journal of molecular sciences · 2025Article
- Objective Assessment of Physical Activity in Breast Cancer Survivors: Associations With Adiposity and Metabolic Parameters of Glucose and Insulin-Insights From NHANES.Cancer reports (Hoboken, N.J.) · 2025Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The phosphoinositide 3-kinase (PI3K)-Akt network is tightly controlled by feedback mechanisms that regulate signal flow and ensure signal fidelity. A rapid overshoot in insulin-stimulated recruitment of Akt to the plasma membrane has previously been reported, which is indicative of negative feedback operating on acute timescales. Here, we show that Akt itself engages this negative feedback by phosphorylating insulin receptor substrate (IRS) 1 and 2 on a number of residues. Phosphorylation results in the depletion of plasma membrane-localised IRS1/2, reducing the pool available for interaction with the insulin receptor. Together these events limit plasma membrane-associated PI3K and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) synthesis. We identified two Akt-dependent phosphorylation sites in IRS2 at S306 (S303 in mouse) and S577 (S573 in mouse) that are key drivers of this negative feedback. These findings establish a novel mechanism by which the kinase Akt acutely controls PIP3 abundance, through post-translational modification of the IRS scaffold.
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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.