ArticleThe Journal of biological chemistry2015
Kinome Screen Identifies PFKFB3 and Glucose Metabolism as Important Regulators of the Insulin/Insulin-like Growth Factor (IGF)-1 Signaling Pathway.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Acute effects of active breaks during prolonged sitting on subcutaneous adipose tissue gene expression: an ancillary analysis of a randomised controlled trial.Scientific reports · 2019Trial
- A cell-based assay for retinaldehyde dehydrogenase activity: Retinoid quantification as an alternative to current fluorescence-based approaches.The Journal of biological chemistry · 2026Article
- Ketone bodies mitigate against systemic inflammation-induced changes in brain energy metabolism and delirium-like deficits in aged mice.bioRxiv : the preprint server for biology · 2026Article
- The multifunctional role of bovine colostrum in managing diabetes: clinical insights and potential therapeutic effects.Journal of diabetes and metabolic disorders · 2025Review
- The insulin signalling network.Nature metabolism · 2025Review
- Depletion of IGFALS Serum Level up to 3 Months After Cardiac Surgery, with Exploration of Potential Relationships to Surrogates of Organ Failures and Clinical Outcomes.Current issues in molecular biology · 2025Article
- Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic Glycolysis.Biomolecules · 2025Article
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
- CHC22 clathrin recruitment to the early secretory pathway requires two-site interaction with SNX5 and p115.The EMBO journal · 2024Article
- Article
- Altered Metabolism and Inflammation Driven by Post-translational Modifications in Intervertebral Disc Degeneration.Research (Washington, D.C.) · 2024Article
- The role of targeting glucose metabolism in chondrocytes in the pathogenesis and therapeutic mechanisms of osteoarthritis: a narrative review.Frontiers in endocrinology · 2024Review
- Article
- Integrating adipocyte insulin signaling and metabolism in the multi-omics era.Trends in biochemical sciences · 2022Review
- Is Estrogen a Missing Culprit in Thyroid Eye Disease? Sex Steroid Hormone Homeostasis Is Key to Other Fibrogenic Autoimmune Diseases - Why Not This One?Frontiers in immunology · 2022Article
- The aetiology and molecular landscape of insulin resistance.Nature reviews. Molecular cell biology · 2021Review
- Hepatocyte-SpecificNutrients · 2021Article
- PFKFB3-dependent glucose metabolism regulates 3T3-L1 adipocyte development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer.International journal of molecular sciences · 2021Review
- Deregulation of angiopoietin-like 4 slows ovarian cancer progression through vascular endothelial growth factor receptor 2 phosphorylation.Cancer cell international · 2021Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The insulin/insulin-like growth factor (IGF)-1 signaling pathway (ISP) plays a fundamental role in long term health in a range of organisms. Protein kinases including Akt and ERK are intimately involved in the ISP. To identify other kinases that may participate in this pathway or intersect with it in a regulatory manner, we performed a whole kinome (779 kinases) siRNA screen for positive or negative regulators of the ISP, using GLUT4 translocation to the cell surface as an output for pathway activity. We identified PFKFB3, a positive regulator of glycolysis that is highly expressed in cancer cells and adipocytes, as a positive ISP regulator. Pharmacological inhibition of PFKFB3 suppressed insulin-stimulated glucose uptake, GLUT4 translocation, and Akt signaling in 3T3-L1 adipocytes. In contrast, overexpression of PFKFB3 in HEK293 cells potentiated insulin-dependent phosphorylation of Akt and Akt substrates. Furthermore, pharmacological modulation of glycolysis in 3T3-L1 adipocytes affected Akt phosphorylation. These data add to an emerging body of evidence that metabolism plays a central role in regulating numerous biological processes including the ISP. Our findings have important implications for diseases such as type 2 diabetes and cancer that are characterized by marked disruption of both metabolism and growth factor signaling.
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