ArticleThe Biochemical journal2018
Stromal cell-derived factor-1 (CXCL12) activates integrins by direct binding to an allosteric ligand-binding site (site 2) of integrins without CXCR4.
Article in The Biochemical journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 44 citations in OpenAlex.
- 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
- Progressive fibrosis in human MASLD is associated with spatially linked transcriptomic signatures of metabolic reprogramming and senescence.JHEP reports : innovation in hepatology · 2026Article
- PF4 Autoantibody Complexes Cause Activation of Integrins αIIbβ3 and αvβ3 and Possible Subsequent Thrombosis and Autoimmune Diseases.International journal of molecular sciences · 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
- Article
- Tenascin-C regulates CXCR4Frontiers in immunology · 2025Article
- Structural insights into the molecular recognition of integrin αVβ3 by RGD-containing ligands: The role of the specificity-determining loop (SDL).bioRxiv : the preprint server for biology · 2024Article
- FGF1 Suppresses Allosteric Activation of β3 Integrins by FGF2: A Potential Mechanism of Anti-Inflammatory and Anti-Thrombotic Action of FGF1.Biomolecules · 2024Article
- Review
- Article
- The C-type lectin domain of CD62P (P-selectin) functions as an integrin ligand.Life science alliance · 2023Article
- Cancer cell-derived novel periostin isoform promotes invasion in head and neck squamous cell carcinoma.Cancer medicine · 2023Article
- Heparin Mimetics and Their Impact on Extracellular Matrix Protein Assemblies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- An expression and function analysis of the CXCR4/SDF-1 signalling axis during pituitary gland development.PloS one · 2023Article
- Article
- Microglia contribute to the postnatal development of cortical somatostatin-positive inhibitory cells and to whisker-evoked cortical activity.Cell reports · 2022Article
- Novel Functions of Integrins as Receptors of CD154: Their Role in Inflammation and Apoptosis.Cells · 2022Review
- Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics.Nature communications · 2022Article
- Biological Therapies in the Treatment of Cancer-Update and New Directions.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Leukocyte arrest on the endothelial cell surface during leukocyte extravasation is induced by rapid integrin activation by chemokines. We recently reported that fractalkine induces integrin activation without its receptor CX3CR1 through binding to the allosteric site (site 2) of integrins. Peptides from site 2 bound to fractalkine and suppressed integrin activation by fractalkine. We hypothesized that this is not limited to membrane-bound fractalkine. We studied whether stromal cell-derived factor-1 (SDF1), another chemokine that plays a critical role in leukocyte arrest, activates integrins through binding to site 2. We describe here that (1) SDF1 activated soluble integrin αvβ3 in cell-free conditions, suggesting that SDF1 can activate αvβ3 without CXCR4; (2) site 2 peptide bound to SDF1, suggesting that SDF1 binds to site 2; (3) SDF1 activated integrins αvβ3, α4β1, and α5β1 on CHO cells (CXCR4-negative) and site 2 peptide suppressed the activation; (4) A CXCR4 antagonist AMD3100 did not affect the site 2-mediated integrin activation by SDF1; (5) Cell-surface integrins were fully activated in 1 min (much faster than activation of soluble αvβ3) and the activation lasted at least for 1 h. We propose that the binding of SDF1 to cell-surface proteoglycan facilitates the allosteric activation process; (6) Mutations in the predicted site 2-binding site in SDF1 suppressed integrin activation. These results suggest that SDF1 (e.g. presented on proteoglycans) can rapidly activate integrins in an allosteric manner by binding to site 2 in the absence of CXCR4. The allosteric integrin activation by SDF1 is a novel target for drug discovery.
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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.