ArticleNature communications2017
LFA-1 activates focal adhesion kinases FAK1/PYK2 to generate LAT-GRB2-SKAP1 complexes that terminate T-cell conjugate formation.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 36 citations in OpenAlex.
- Multiple sclerosis-associated CD226 variant disrupts vitamin D-induced type I Treg differentiation by impairing LFA-1 activation.The Journal of clinical investigation · 2026Article
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- Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.Science advances · 2025Article
- Identification of hub genes and transcription factors in patients with primary gout complicated with atherosclerosis.Scientific reports · 2024Article
- Review
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- Multi-functional adaptor SKAP1: regulator of integrin activation, the stop-signal, and the proliferation of T cells.Frontiers in immunology · 2023Review
- Immune cells and their related genes provide a new perspective on the common pathogenesis of ankylosing spondylitis and inflammatory bowel diseases.Frontiers in immunology · 2023Article
- LFA-1 in T cell priming, differentiation, and effector functions.Trends in immunology · 2021Review
- Irisin supports integrin-mediated cell adhesion of lymphocytes.Biochemistry and biophysics reports · 2021Article
- Targeting FAK in anticancer combination therapies.Nature reviews. Cancer · 2021Review
- Optical Control of CD8Frontiers in immunology · 2021Article
- Identification of Gene Co-Expression Modules and Core Genes Related to Immune Disorders in Major Depression Disorder.International journal of general medicine · 2021Article
- How the Discovery of the CD4/CD8-p56Frontiers in cell and developmental biology · 2021Review
- The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events.Frontiers in immunology · 2021Review
- LFA-1 signals to promote actin polymerization and upstream migration in T cells.Journal of cell science · 2020Article
- SKAP2 is required for defense againsteLife · 2020Article
- Loss of BAP1 expression is associated with an immunosuppressive microenvironment in uveal melanoma, with implications for immunotherapy development.The Journal of pathology · 2020Article
- GTPase-activating protein Rasal1 associates with ZAP-70 of the TCR and negatively regulates T-cell tumor immunity.Nature communications · 2019Article
- Differential nanoscale organisation of LFA-1 modulates T-cell migration.Journal of cell science · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Lymphocyte function-associated antigen 1 (LFA-1) affinity and avidity changes have been assumed to mediate adhesion to intercellular adhesion molecule-1 for T-cell conjugation to dendritic cells (DC). Although the T-cell receptor (TCR) and LFA-1 can generate intracellular signals, the immune cell adaptor protein linker for the activation of T cells (LAT) couples the TCR to downstream events. Here, we show that LFA-1 can mediate both adhesion and de-adhesion, dependent on receptor clustering. Although increased affinity mediates adhesion, LFA-1 cross-linking induced the association and activation of the protein-tyrosine kinases FAK1/PYK1 that phosphorylated LAT selectively on a single Y-171 site for the binding to adaptor complex GRB-2-SKAP1. LAT-GRB2-SKAP1 complexes were distinct from canonical LAT-GADs-SLP-76 complexes. LFA-1 cross-linking increased the presence of LAT-GRB2-SKAP1 complexes relative to LAT-GADs-SLP-76 complexes. LFA-1-FAK1 decreased T-cell-dendritic cell (DC) dwell times dependent on LAT-Y171, leading to reduced DO11.10 T cell binding to DCs and proliferation to OVA peptide. Overall, our findings outline a new model for LFA-1 in which the integrin can mediate both adhesion and de-adhesion events dependent on receptor cross-linking.
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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.