ArticleProceedings of the National Academy of Sciences of the United States of America2003
Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers.
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Who cites it
179 citing papers in PubMed, 423 citations in OpenAlex.
- Regulation of reticular adhesions by KANK2 and talin2 in two melanoma cell lines.Cell communication and signaling : CCS · 2026Article
- Development and characterization of an inducible Tensin1 deficient transgenic murine model.Scientific reports · 2026Article
- Dual recruitment of two CCM2 molecules to KRIT1 suppresses KLF4 expression.Nature communications · 2026Article
- FCHo2, not talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.Nature communications · 2026Article
- Talin-tensin3 interactions regulate fibrillar adhesion formation and tensin3 phase separation.The Journal of cell biology · 2026Article
- Characterization of Membrane Binding and Protein-Lipid Interactions at the Atomic Level with an Accelerated HMMM Model.Methods in molecular biology (Clifton, N.J.) · 2026Article
- FCHo2, instead of talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.bioRxiv : the preprint server for biology · 2025Article
- Spatial N-glycan rearrangement on αNature communications · 2025Article
- Allosteric Disulfide Bridges in Integrins: The Molecular Switches of Redox Regulation of Integrin-Mediated Cell Functions.Antioxidants (Basel, Switzerland) · 2025Review
- Tensins in Cancer: Integration of Their Domain Functions, Context-Dependent Regulation and Biomarker Potential.Biology · 2025Review
- Kindlin Regulates Mechanosensitive Activation and Adhesion Assembly of Integrin beta6.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dynamic regulation of integrin β1 phosphorylation supports invasion of breast cancer cells.Nature cell biology · 2025Article
- Tensin-2 interactomics reveals interaction with GAPDH and a phosphorylation-mediated regulatory role in glycolysis.Scientific reports · 2024Article
- Integrating integrins with the hallmarks of cancer.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- Producing highly effective extracellular vesicles using IBAR and talin F3 domain fusion.Animal cells and systems · 2024Article
- Identification of Tensin-3 as a MALT1 substrate that controls B cell adhesion and lymphoma dissemination.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Immunohistochemical Expression of Tensin-4/CTEN in Squamous Cell Carcinoma in Dogs.Veterinary sciences · 2023Article
- The role of tensins in malignant neoplasms.Archives of medical science : AMS · 2023Article
- Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4).Communications biology · 2022Article
- Review
119 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytoplasmic domains (tails) of heterodimeric integrin adhesion receptors mediate integrins' biological functions by binding to cytoplasmic proteins. Most integrin beta tails contain one or two NPXYF motifs that can form beta turns. These motifs are part of a canonical recognition sequence for phosphotyrosine-binding (PTB) domains, protein modules that are present in a wide variety of signaling and cytoskeletal proteins. Indeed, talin and ICAP1-alpha bind to integrin beta tails by means of a PTB domain-NPXY ligand interaction. To assess the generality of this interaction we examined the binding of a series of recombinant PTB domains to a panel of short integrin beta tails. In addition to the known integrin-binding proteins, we found that Numb (a negative regulator of Notch signaling) and Dok-1 (a signaling adaptor involved in cell migration) and their isolated PTB domain bound to integrin tails. Furthermore, Dok-1 physically associated with integrin alpha IIb beta 3. Mutations of the integrin beta tails confirmed that these interactions are canonical PTB domain-ligand interactions. First, the interactions were blocked by mutation of an NPXY motif in the integrin tail. Second, integrin class-specific interactions were observed with the PTB domains of Dab, EPS8, and tensin. We used this specificity, and a molecular model of an integrin beta tail-PTB domain interaction to predict critical interacting residues. The importance of these residues was confirmed by generation of gain- and loss-of-function mutations in beta 7 and beta 3 tails. These data establish that short integrin beta tails interact with a large number of PTB domain-containing proteins through a structurally conserved mechanism.
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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.