ArticleNature communications2015
PI3K-C2γ is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 174 citations in OpenAlex.
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- Complex interactions between miR-107 and PTEN gene expression, more specifically in viral and NASH cirrhosis.Biochemistry and biophysics reports · 2026Article
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- PFAS Exposure and Metabolic Disorders: Mechanistic Insights into Lipid and Glucose Homeostasis.Biomolecules · 2026Review
- Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Review
- Revisiting AI Interpretability in Precision Oncology: Why Predictive Accuracy Does Not Ensure Stable Feature Importance.Cancers · 2026Article
- Maternal Nutrient Restriction Programs Fetal Hepatic DNA Methylation in Ovine Monozygotic Twins.International journal of molecular sciences · 2026Article
- Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways.Clinical science (London, England : 1979) · 2025Review
- Implications of Altered Endosomal-Lysosomal Biogenesis in Melanoma Pathogenesis.International journal of molecular sciences · 2025Review
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- Endosomal HAntioxidants (Basel, Switzerland) · 2025Article
- Functional impact of splicing variants in the elaboration of complex traits in cattle.Nature communications · 2025Article
- Non-coding RNAs and regulation of the PI3K signaling pathway in lung cancer: Recent insights and potential clinical applications.Non-coding RNA research · 2025Review
- PTPN23-dependent activation of PI3KC2α is a therapeutic vulnerability of BRAF-mutant cancers.The Journal of experimental medicine · 2025Article
- Inositol metabolism as a broad-spectrum antiviral target.Frontiers in microbiology · 2025Review
- Targeting PI3K family with small-molecule inhibitors in cancer therapy: current clinical status and future directions.Molecular cancer · 2024Review
- Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation‑mediating treatment options (Review).Molecular medicine reports · 2024Review
- Akt may associate with insulin-responsive vesicles via interaction with sortilin.FEBS letters · 2024Article
- Endothelial Dysfunction in Obesity and Therapeutic Targets.Advances in experimental medicine and biology · 2024Review
- Structural Basis for Highly Selective Class II Alpha Phosphoinositide-3-Kinase Inhibition.Journal of medicinal chemistry · 2023Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
In the liver, insulin-mediated activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is at the core of metabolic control. Multiple PI3K and Akt isoenzymes are found in hepatocytes and whether isoform-selective interplays exist is currently unclear. Here we report that insulin signalling triggers the association of the liver-specific class II PI3K isoform γ (PI3K-C2γ) with Rab5-GTP, and its recruitment to Rab5-positive early endosomes. In these vesicles, PI3K-C2γ produces a phosphatidylinositol-3,4-bisphosphate pool specifically required for delayed and sustained endosomal Akt2 stimulation. Accordingly, loss of PI3K-C2γ does not affect insulin-dependent Akt1 activation as well as S6K and FoxO1-3 phosphorylation, but selectively reduces Akt2 activation, which specifically inhibits glycogen synthase activity. As a consequence, PI3K-C2γ-deficient mice display severely reduced liver accumulation of glycogen and develop hyperlipidemia, adiposity as well as insulin resistance with age or after consumption of a high-fat diet. Our data indicate PI3K-C2γ supports an isoenzyme-specific forking of insulin-mediated signal transduction to an endosomal pool of Akt2, required for glucose homeostasis.
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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.