ArticleCell discovery2022
Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes.
Article in Cell discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- Novel perspectives on PPARγ regulation: from SPPARMs to the emerging role of lncRNAs in metabolic disorders.International journal of obesity (2005) · 2026Review
- AKT1 phosphorylates PRMT7 to promote GLUD1 methylation and gastric cancer progression.Cell death & disease · 2026Article
- Label-free imaging of intracellular structures in living mammalian cells via external apodization phase-contrast microscopy.The FEBS journal · 2026Article
- Golgi-associated TRAF6 as a regulator of protein convertase FURIN for insulin receptor precursor processing.Science China. Life sciences · 2025Article
- CpG-A induces liquid-liquid phase separation of HMGB1 to activate the RAGE-mediated inflammatory pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- PRAG1 Condensation Drives Cell Contraction Under Stress.Biomolecules · 2025Article
- Artesunate: A Review of Its Potential Therapeutic Effects and Mechanisms in Digestive Diseases.Pharmaceutics · 2025Review
- PEX11B palmitoylation couples peroxisomal dysfunction with Schwann cells fail in diabetic neuropathy.Journal of biomedical science · 2025Article
- KPNA3 regulates histone locus body formation by modulating condensation and nuclear import of NPAT.The Journal of cell biology · 2025Article
- Technologies for studying phase-separated biomolecular condensates.Advanced biotechnology · 2024Review
- Protein nanocondensates: the next frontier.Biophysical reviews · 2023Review
- VAPB-mediated ER-targeting stabilizes IRS-1 signalosomes to regulate insulin/IGF signaling.Cell discovery · 2023Article
- Role of condensates in modulating DNA repair pathways and its implication for chemoresistance.The Journal of biological chemistry · 2023Review
- A novel view of the insulin signaling pathway based on prediction of protein structure by the AI platform AlphaFold.Journal of diabetes investigation · 2023Article
- Research progress of dihydromyricetin in the treatment of diabetes mellitus.Frontiers in endocrinology · 2023Review
- The dynamic clustering of insulin receptor underlies its signaling and is disrupted in insulin resistance.Nature communications · 2022Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
As a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. A long and unstructured C-terminal region of IRS-1 recruits downstream effectors for promoting insulin/IGF signals. However, the underlying molecular basis for this remains elusive. Here, we found that the C-terminus of IRS-1 undergoes liquid-liquid phase separation (LLPS). Both electrostatic and hydrophobic interactions were seen to drive IRS-1 LLPS. Self-association of IRS-1, which was mainly mediated by the 301-600 region, drives IRS-1 LLPS to form insulin/IGF-1 signalosomes. Moreover, tyrosine residues of YXXM motifs, which recruit downstream effectors, also contributed to IRS-1 self-association and LLPS. Impairment of IRS-1 LLPS attenuated its positive effects on insulin/IGF-1 signaling. The metabolic disease-associated G972R mutation impaired the self-association and LLPS of IRS-1. Our findings delineate a mechanism in which LLPS of IRS-1-mediated signalosomes serves as an organizing center for insulin/IGF-1 signaling and implicate the role of aberrant IRS-1 LLPS in metabolic diseases.
Identifiers
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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.