ArticleeLife2018
IRS-1 acts as an endocytic regulator of IGF-I receptor to facilitate sustained IGF signaling.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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
40 citing papers in PubMed, 59 citations in OpenAlex.
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- Endocytic turnover of endothelial cell-membrane proteins as a driver of rat blood-brain barrier specialization and dysfunction.iScience · 2026Article
- Paracrine signals from HIV-1-infected immune cells reprogram cervical cancer pathways.iScience · 2026Article
- ClinASO: An open-source platform for rapid drug discovery of gapmer antisense oligonucleotides.Molecular therapy. Nucleic acids · 2026Article
- Divergent Roles of Zebrafish IGF1 Receptor a and b in Glucose and Lipid Metabolism.International journal of molecular sciences · 2026Article
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- Multiomics transcriptome and metabolome insights into fat metabolism and meat quality in Songliao black pigs and Songlei crossbred pigs.BMC genomics · 2026Article
- Characterizing longitudinal patterns of central and peripheral insulin resistance.Psychoneuroendocrinology · 2025Article
- Live-Cell NanoBRET Assay to Measure AKT Inhibitor Binding to Conformational States of AKT.ACS chemical biology · 2025Article
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
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- Chicken Primordial Germ Cells Do Not Proliferate in Insulin-Lacking Media.International journal of molecular sciences · 2025Article
- Targeting Surface Markers in Anaplastic Thyroid Cancer: Future Directions in Ligand-bound Therapy.Journal of the Endocrine Society · 2025Review
- Fenvalerate exposure induces AKT/AMPK-dependent alterations in glucose metabolism in hepatoma cells.Frontiers in pharmacology · 2025Article
- Association between Insulin-Like Growth Factor Binding Protein-7 and Heart Failure.Current medicinal chemistry · 2025Review
- IGF-I concentration determines cell fate by converting signaling dynamics as a bifurcation parameter in L6 myoblasts.Scientific reports · 2024Article
- Is It Possible to Train the Endothelium?-A Narrative Literature Review.Life (Basel, Switzerland) · 2024Review
- A viral insulin-like peptide inhibits IGF-1 receptor phosphorylation and regulates IGF1R gene expression.Molecular metabolism · 2024Article
- Genomic characterization of an esthesioneuroblastoma with spinal metastases: illustrative case.Journal of neurosurgery. Case lessons · 2023Article
- IGF-1R targeting in cancer - does sub-cellular localization matter?Journal of experimental & clinical cancer research : CR · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin-like growth factor-I receptor (IGF-IR) preferentially regulates the long-term IGF activities including growth and metabolism. Kinetics of ligand-dependent IGF-IR endocytosis determines how IGF induces such downstream signaling outputs. Here, we find that the insulin receptor substrate (IRS)-1 modulates how long ligand-activated IGF-IR remains at the cell surface before undergoing endocytosis in mammalian cells. IRS-1 interacts with the clathrin adaptor complex AP2. IRS-1, but not an AP2-binding-deficient mutant, delays AP2-mediated IGF-IR endocytosis after the ligand stimulation. Mechanistically, IRS-1 inhibits the recruitment of IGF-IR into clathrin-coated structures; for this reason, IGF-IR avoids rapid endocytosis and prolongs its activity on the cell surface. Accelerating IGF-IR endocytosis via IRS-1 depletion induces the shift from sustained to transient Akt activation and augments FoxO-mediated transcription. Our study establishes a new role for IRS-1 as an endocytic regulator of IGF-IR that ensures sustained IGF bioactivity, independent of its classic role as an adaptor in IGF-IR signaling.
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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.