ArticleNature communications2024
Activation of the insulin receptor by insulin-like growth factor 2.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Insulin mimetics and non-canonical insulin receptor signaling: mechanisms and disease relevance.Experimental & molecular medicine · 2026Review
- Insulin-like growth factor-binding protein 7 is a soluble cell adhesion molecule.Science advances · 2026Article
- Pan-filovirus activity of an IGF2-fused monoclonal antibody: Impairment by IGF1R cross-engagement and rescue via IGF2 Y27L mutation.Virus research · 2026Article
- An engineered insulin analog with dual insulin and IGF-1 receptor agonism and distinct signaling.Science advances · 2026Article
- Reprogramming insulin receptor activation with a de novo agonist to overcome severe insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- Insulin-like growth factor 2 as a central regulator of growth and metabolic efficiency in livestock: Genetic, nutritional, and biotechnological perspectives.Veterinary world · 2026Review
- Insulin resistance: mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Article
- Mutation in IR or IGF1R produces features of long-lived mice while maintaining metabolic health.JCI insight · 2025Article
- Tuning insulin receptor signaling using de novo-designed agonists.Molecular cell · 2025Article
- Domain-substituted IGF2 tag modulates targeting of lentiviral gene therapy for Hunter syndrome.EMBO molecular medicine · 2025Article
- Structure and activation of the Drosophila insulin receptor by three Drosophila insulin-like peptides.Nature communications · 2025Article
- The insulin-like peptides Dilp2 and Dilp6 exhibit divergent responses to dietary sugar and protein inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Paradoxical regulation of IGF2 in promoting lipid metabolism in adipose tissues.Communications biology · 2025Article
- Pig Taste Cell-derived Organoids Synthesize Insulin.Endocrinology · 2025Article
- Structural mechanism of insulin receptor activation by a dimeric aptamer agonist.Experimental & molecular medicine · 2025Article
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- The Hypoglycemic Activity ofGels (Basel, Switzerland) · 2025Article
- Insulin-Like Growth Factor Signaling in Alzheimer's Disease: Pathophysiology and Therapeutic Strategies.Molecular neurobiology · 2025Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Insulin receptor (IR) controls growth and metabolism. Insulin-like growth factor 2 (IGF2) has different binding properties on two IR isoforms, mimicking insulin's function. However, the molecular mechanism underlying IGF2-induced IR activation remains unclear. Here, we present cryo-EM structures of full-length human long isoform IR (IR-B) in both the inactive and IGF2-bound active states, and short isoform IR (IR-A) in the IGF2-bound active state. Under saturated IGF2 concentrations, both the IR-A and IR-B adopt predominantly asymmetric conformations with two or three IGF2s bound at site-1 and site-2, which differs from that insulin saturated IR forms an exclusively T-shaped symmetric conformation. IGF2 exhibits a relatively weak binding to IR site-2 compared to insulin, making it less potent in promoting full IR activation. Cell-based experiments validated the functional importance of IGF2 binding to two distinct binding sites in optimal IR signaling and trafficking. In the inactive state, the C-terminus of α-CT of IR-B contacts FnIII-2 domain of the same protomer, hindering its threading into the C-loop of IGF2, thus reducing the association rate of IGF2 with IR-B. Collectively, our studies demonstrate the activation mechanism of IR by IGF2 and reveal the molecular basis underlying the different affinity of IGF2 to IR-A and IR-B.
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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.