ArticleThe Journal of biological chemistry2009
Beta integrin tyrosine phosphorylation is a conserved mechanism for regulating talin-induced integrin activation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 127 citations in OpenAlex.
- FCHo2, not talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.Nature communications · 2026Article
- FCHo2, instead of talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.bioRxiv : the preprint server for biology · 2025Article
- The phosphatase PPM1F, a negative regulator of integrin activity, is essential for embryonic development and controls tumor cell invasion.BMC biology · 2025Article
- Revisiting nephrin signaling and its specialized effects on the uniquely adaptable podocyte.The Biochemical journal · 2025Review
- Dynamic regulation of integrin β1 phosphorylation supports invasion of breast cancer cells.Nature cell biology · 2025Article
- Quantitative Glycan-Protein Cross-Linking Mass Spectrometry Using Enrichable Linkers Reveals Extensive Glycan-Mediated Protein Interaction Networks.Analytical chemistry · 2025Article
- Acetyl-NPKY of integrin-β1 binds KINDLIN2 to control endothelial cell proliferation and junctional integrity.iScience · 2024Article
- Review
- High-resolution structure of a fish aquaporin reveals a novel extracellular fold.Life science alliance · 2022Article
- The structural basis of β2 integrin intra-cellular multi-protein complexes.Biophysical reviews · 2022Review
- New insights into the phosphorylation of the threonine motif of the β1 integrin cytoplasmic domain.Life science alliance · 2022Article
- Adhesion ofFrontiers in cell and developmental biology · 2022Review
- c-Met-integrin cooperation: Mechanisms, tumorigenic effects, and therapeutic relevance.Frontiers in cell and developmental biology · 2022Review
- Proteome-scale mapping of binding sites in the unstructured regions of the human proteome.Molecular systems biology · 2022Article
- A CD22-Shp1 phosphatase axis controls integrin βNature immunology · 2021Article
- Talin-dependent integrin activation is required for endothelial proliferation and postnatal angiogenesis.Angiogenesis · 2021Article
- PTP-3 phosphatase promotes intramolecular folding of SYD-2 to inactivate kinesin-3 UNC-104 in neurons.Molecular biology of the cell · 2020Article
- PPM1F controls integrin activity via a conserved phospho-switch.The Journal of cell biology · 2020Article
- Talin and Kindlin as Integrin-Activating Proteins: Focus on the Heart.Pediatric cardiology · 2019Review
- Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting.Journal of hematology & oncology · 2019Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Integrins are large membrane-spanning receptors fundamental to cell adhesion and migration. Integrin adhesiveness for the extracellular matrix is activated by the cytoskeletal protein talin via direct binding of its phosphotyrosine-binding-like F3 domain to the cytoplasmic tail of the beta integrin subunit. The phosphotyrosine-binding domain of the signaling protein Dok1, on the other hand, has an inactivating effect on integrins, a phenomenon that is modulated by integrin tyrosine phosphorylation. Using full-length tyrosine-phosphorylated (15)N-labeled beta3, beta1A, and beta7 integrin tails and an NMR-based protein-protein interaction assay, we show that talin1 binds to the NPXY motif and the membrane-proximal portion of beta3, beta1A, and beta7 tails, and that the affinity of this interaction is decreased by integrin tyrosine phosphorylation. Dok1 only interacts weakly with unphosphorylated tails, but its affinity is greatly increased by integrin tyrosine phosphorylation. The Dok1 interaction remains restricted to the integrin NPXY region, thus phosphorylation inhibits integrin activation by increasing the affinity of beta integrin tails for a talin competitor that does not form activating membrane-proximal interactions with the integrin. Key residues governing these specificities were identified by detailed structural analysis, and talin1 was engineered to bind preferentially to phosphorylated integrins by introducing the mutation D372R. As predicted, this mutation affects talin1 localization in live cells in an integrin phosphorylation-specific manner. Together, these results indicate that tyrosine phosphorylation is a common mechanism for regulating integrin activation, despite subtle differences in how these integrins interact with their binding proteins.
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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.