ArticleThe Journal of cell biology1994
Integrin cytoplasmic domains mediate inside-out signal transduction.
Article in The Journal of cell biology, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers.
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Who cites it
184 citing papers in PubMed, 672 citations in OpenAlex.
- MnBiophysical journal · 2025Article
- Integrin signalling in joint development, homeostasis and osteoarthritis.Nature reviews. Rheumatology · 2024Review
- Itga5-PTEN signaling regulates striatal synaptic strength and motor coordination in Parkinson's disease.International journal of biological sciences · 2024Article
- Kindlin2 enables EphB/ephrinB bi-directional signaling to support vascular development.Life science alliance · 2023Article
- Phostensin enables lymphocyte integrin activation and population of peripheral lymphoid organs.The Journal of experimental medicine · 2022Article
- The Capillary Morphogenesis Gene 2 Triggers the Intracellular Hallmarks of Collagen VI-Related Muscular Dystrophy.International journal of molecular sciences · 2022Article
- Integrin intra-heterodimer affinity inversely correlates with integrin activatability.Cell reports · 2021Article
- Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding.The Journal of biological chemistry · 2020Article
- Article
- Molecular determinants of mesenchymal cell activation in fibroproliferative diseases.Cellular and molecular life sciences : CMLS · 2019Review
- Integrin α11 cytoplasmic tail is required for FAK activation to initiate 3D cell invasion and ERK-mediated cell proliferation.Scientific reports · 2019Article
- Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem.The Journal of cell biology · 2019Article
- Kindlin-2 interacts with a highly conserved surface of ILK to regulate focal adhesion localization and cell spreading.Journal of cell science · 2018Article
- Role of Extracellular Matrix in Development and Cancer Progression.International journal of molecular sciences · 2018Review
- Rap1 binding to the talin 1 F0 domain makes a minimal contribution to murine platelet GPIIb-IIIa activation.Blood advances · 2018Article
- Phosphorylation of the α-chain in the integrin LFA-1 enables β2-chain phosphorylation and α-actinin binding required for cell adhesion.The Journal of biological chemistry · 2018Article
- On the contributing role of the transmembrane domain for subunit-specific sensitivity of integrin activation.Scientific reports · 2018Article
- The membrane-distal regions of integrin α cytoplasmic domains contribute differently to integrin inside-out activation.Scientific reports · 2018Article
- Nuclear Localization of Integrin Cytoplasmic Domain-associated Protein-1 (ICAP1) Influences β1 Integrin Activation and Recruits Krev/Interaction Trapped-1 (KRIT1) to the Nucleus.The Journal of biological chemistry · 2017Article
- Mechanical Control of Myotendinous Junction Formation and Tendon Differentiation during Development.Frontiers in cell and developmental biology · 2017Review
124 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
Abstract
We analyzed the binding of fibronectin to integrin alpha 5 beta 1 in various cells; in some cells fibronectin bound with low affinity (e.g., K562 cells) whereas in others (e.g., CHO), it bound with high affinity (Kd approximately 100 nM) in an energy-dependent manner. We constructed chimeras of the extracellular and transmembrane domains of alpha IIb beta 3 joined to the cytoplasmic domains of alpha 5 beta 1. The affinity state of these chimeras was assessed by binding of fibrinogen or the monoclonal antibody, PAC1. The cytoplasmic domains of alpha 5 beta 1 conferred an energy-dependent high affinity state on alpha IIb beta 3 in CHO but not K562 cells. Three additional alpha cytoplasmic domains (alpha 2, alpha 6A, alpha 6B) conferred PAC1 binding in CHO cells, while three others (alpha M, alpha L, alpha v) did not. In the high affinity alpha chimeras, cotransfection with a truncated (beta 3 delta 724) or mutated (beta 3(S752-->P)) beta 3 subunit abolished high affinity binding. Thus, both cytoplasmic domains are required for energy-dependent, cell type-specific affinity modulation. In addition, mutations that disrupted a highly conserved alpha subunit GFFKR motif, resulted in high affinity binding of ligands to alpha IIb beta 3. In contrast to the chimeras, the high affinity state of these mutants was independent of cellular metabolism, cell type, and the bulk of the beta subunit cytoplasmic domain. Thus, integrin cytoplasmic domains mediate inside-out signaling. Furthermore, the highly conserved GFFKR motif of the alpha subunit cytoplasmic domain maintains the default low affinity state.
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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.