ArticleThe Journal of biological chemistry2010
Direct binding of the EGF-like domain of neuregulin-1 to integrins ({alpha}v{beta}3 and {alpha}6{beta}4) is involved in neuregulin-1/ErbB signaling.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 100 citations in OpenAlex.
- Plasma proteome profiling identified biomarkers for the differential diagnosis and molecular staging of neurodegenerative dementias.Nature aging · 2026Article
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- Galectin-3 Binds to the Allosteric Site and Activates Integrins αvβ3, αIIbβ3, and α5β1, and Lactose Inhibits This Activation.Biomolecules · 2026Article
- Galectin-3 binds to the RGD-binding site in a glycan-independent manner and to the allosteric site and activates integrins αvβ3, αIIbβ3, and α5β1.bioRxiv : the preprint server for biology · 2026Article
- Single-Cell Transcriptomic Landscape of Cervical Cancer Cell Lines Before and After Chemoradiotherapy.Cells · 2026Article
- EGFL6 is a novel HER3 ligand, inducing HER3/integrin heterodimers to induce pERK centrosomal deposition and therapeutic resistance.Neoplasia (New York, N.Y.) · 2025Article
- Laminin Receptors in Peripheral Tissues: Functions Revealed by Analysis of Knockout Mice.The American journal of pathology · 2025Review
- A new gut pathogenic bacteria and its metabolites promote colorectal cancer development and act as non-invasive early diagnostic biomarkers.Gut microbes · 2025Article
- Ivermectin Binds to the Allosteric Site (Site 2) and Inhibits Allosteric Integrin Activation by TNF and Other Pro-Inflammatory Cytokines.International journal of molecular sciences · 2025Article
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- Modeling the dynamics of EMT reveals genes associated with pan-cancer intermediate states and plasticity.NPJ systems biology and applications · 2025Article
- Neuregulin-1 prevents death from a normally lethal respiratory viral infection.PLoS pathogens · 2025Article
- Genomically Selected Genes Associated with a High Rate of Egg Production in Puan Panjiang Black-Bone Chickens.Animals : an open access journal from MDPI · 2025Article
- Cytokine Expression Profiling in Idiopathic Pulmonary Fibrosis: Insights From Integrative Proteomic Analysis.Canadian respiratory journal · 2025Article
- Talin1 promotes HCC progression by regulating NRG1/PI3K/AKT pathway.Discover oncology · 2024Article
- FGF1 Suppresses Allosteric Activation of β3 Integrins by FGF2: A Potential Mechanism of Anti-Inflammatory and Anti-Thrombotic Action of FGF1.Biomolecules · 2024Article
- Adipocyte Precursor-Derived NRG1 Promotes Resistance to FGFR Inhibition in Urothelial Carcinoma.Cancer research · 2024Article
- The heparin-binding domain of VEGF165 directly binds to integrin αvβ3 and VEGFR2/KDR D1: a potential mechanism of negative regulation of VEGF165 signaling by αvβ3.Frontiers in cell and developmental biology · 2024Article
- Nidogen-1/NID1 Function and Regulation during Progression and Metastasis of Colorectal Cancer.Cancers · 2023Article
- Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Integrin-growth factor receptor cross-talk plays a role in growth factor signaling, but the specifics are unclear. In a current model, integrins and growth factor receptors independently bind to their ligands (extracellular matrix and growth factors, respectively). We discovered that neuregulin-1 (NRG1), either as an isolated EGF-like domain or as a native multi-domain form, binds to integrins αvβ3 (with a K(D) of 1.36 × 10(-7) m) and α6β4. Docking simulation predicted that three Lys residues at positions 180, 184, and 186 of the EGF-like domain are involved in integrin binding. Mutating these residues to Glu individually or in combination markedly suppressed integrin binding and ErbB3 phosphorylation. Mutating all three Lys residues to Glu (the 3KE mutation) did not affect the ability of NRG1 to bind to ErbB3 but markedly reduced the ability of NRG1 to induce ErbB3 phosphorylation and AKT and Erk1/2 activation in MCF-7 and T47D human breast cancer cells. This suggests that direct integrin binding to NRG1 is critical for NRG1/ErbB signaling. Notably, stimulation of cells with WT NRG1 induced co-precipitation of ErbB3 with α6β4 and with αvβ3 to a much lower extent. This suggests that WT NRG1 induces integrin-NRG1-ErbB3 ternary complex formation. In contrast, the 3KE mutant was much less effective in inducing ternary complex formation than WT NRG1, suggesting that this process depends on the ability of NRG1 to bind to integrins. These results suggest that direct NRG1-integrin interaction mediates integrin-ErbB cross-talk and that α6β4 plays a major role in NRG-ErbB signaling in these cancer cells.
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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.