ArticleProceedings of the National Academy of Sciences of the United States of America2023
A specialized integrin-binding motif enables proTGF-β2 activation by integrin αVβ6 but not αVβ8.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Transforming growth factor-β in kidney disease in dogs and cats: a review of the evidence of its role in renal fibrosis.Journal of veterinary internal medicine · 2026Review
- Eosinophils promote a second wave of postnatal smooth muscle differentiation in intestinal villi.The Journal of cell biology · 2026Article
- Prolonged high-density culture with restricted medium renewal induces epithelial-like plasticity in apical papilla stem cells.Biomolecules & biomedicine · 2026Article
- Role of external forces in the mechanobiology of stem and differentiated chondrogenic cells embedded in a tissue-engineered construct for cartilage repair.Journal of biomedical science · 2026Review
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Latent-TGF-β has a domain swapped architecture.Nature communications · 2025Article
- Structures of TGF-β with betaglycan and signaling receptors reveal mechanisms of complex assembly and signaling.Nature communications · 2025Article
- A divergent two-domain structure of the anti-Müllerian hormone prodomain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Fibroblast and myofibroblast activation in normal tissue repair and fibrosis.Nature reviews. Molecular cell biology · 2024Review
- Molecular Characterization of the Distal Lung: Novel Insights from Chronic Obstructive Pulmonary Disease Omics.American journal of respiratory and critical care medicine · 2024Article
- Binding requirements for latent transforming growth factor Beta2 activation.Matrix biology plus · 2024Article
- Distinct fibroblast functions associated with fibrotic and immune-mediated inflammatory diseases and their implications for therapeutic development.F1000Research · 2024Review
- TGF-β signaling in health and disease.Cell · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of latent transforming growth factor (TGF)-β2 is incompletely understood. Unlike TGF-β1 and β3, the TGF-β2 prodomain lacks a seven-residue RGDLXX (L/I) integrin-recognition motif and is thought not to be activated by integrins. Here, we report the surprising finding that TGF-β2 contains a related but divergent 13-residue integrin-recognition motif (YTSGDQKTIKSTR) that specializes it for activation by integrin αVβ6 but not αVβ8. Both classes of motifs compete for the same binding site in αVβ6. Multiple changes in the longer motif underlie its specificity. ProTGF-β2 structures define interesting differences from proTGF-β1 and the structural context for activation by αVβ6. Some integrin-independent activation is also seen for proTGF-β2 and even more so for proTGF-β3. Our findings have important implications for therapeutics to αVβ6 in clinical trials for fibrosis, in which inhibition of TGF-β2 activation has not been anticipated.
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