ArticleNature communications2019
Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 89 citations in OpenAlex.
- Reprogramming insulin receptor activation with a de novo agonist to overcome severe insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- Insulin receptor trafficking and interactions in muscle cells.Journal of the Endocrine Society · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.EMBO reports · 2026Article
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- Targeting Protein Tyrosine Phosphatases via PROteolysis-TArgeting Chimeras (PROTACs): Current Developments and Prospects.Molecules (Basel, Switzerland) · 2025Review
- Tuning insulin receptor signaling using de novo-designed agonists.Molecular cell · 2025Article
- The insulin signalling network.Nature metabolism · 2025Review
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- Multi-layered proteomics identifies insulin-induced upregulation of the EphA2 receptor via the ERK pathway which is dependent on low IGF1R level.Scientific reports · 2024Article
- CompariPSSM: a PSSM-PSSM comparison tool for motif-binding determinant analysis.Bioinformatics (Oxford, England) · 2024Article
- SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac.Science advances · 2024Article
- The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose.Obesity (Silver Spring, Md.) · 2024Article
- The effect of adipose-derived mesenchymal stem cell transplantation on ovarian mitochondrial dysfunction in letrozole-induced polycystic ovary syndrome in rats: the role of PI3K-AKT signaling pathway.Journal of ovarian research · 2024Article
- Activation of the insulin receptor by insulin-like growth factor 2.Nature communications · 2024Article
- Article
- A viral insulin-like peptide inhibits IGF-1 receptor phosphorylation and regulates IGF1R gene expression.Molecular metabolism · 2024Article
- Article
- The cell cycle protein MAD2 facilitates endocytosis of the serotonin transporter in the neuronal soma.EMBO reports · 2023Article
- Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells.International journal of molecular sciences · 2023Article
- The Activation Mechanism of the Insulin Receptor: A Structural Perspective.Annual review of biochemistry · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin controls glucose homeostasis and cell growth through bifurcated signaling pathways. Dysregulation of insulin signaling is linked to diabetes and cancer. The spindle checkpoint controls the fidelity of chromosome segregation during mitosis. Here, we show that insulin receptor substrate 1 and 2 (IRS1/2) cooperate with spindle checkpoint proteins to promote insulin receptor (IR) endocytosis through recruiting the clathrin adaptor complex AP2 to IR. A phosphorylation switch of IRS1/2 orchestrated by extracellular signal-regulated kinase 1 and 2 (ERK1/2) and Src homology phosphatase 2 (SHP2) ensures selective internalization of activated IR. SHP2 inhibition blocks this feedback regulation and growth-promoting IR signaling, prolongs insulin action on metabolism, and improves insulin sensitivity in mice. We propose that mitotic regulators and SHP2 promote feedback inhibition of IR, thereby limiting the duration of insulin signaling. Targeting this feedback inhibition can improve insulin sensitivity.
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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.