ArticleProceedings of the National Academy of Sciences of the United States of America2009
SLP-76-ADAP adaptor module regulates LFA-1 mediated costimulation and T cell motility.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.American journal of human genetics · 2013Pooled it
- Multiple sclerosis-associated CD226 variant disrupts vitamin D-induced type I Treg differentiation by impairing LFA-1 activation.The Journal of clinical investigation · 2026Article
- A novel adaptor protein, ARAP, orchestrates Fcγ receptor signaling in mouse dendritic cells via Rap1 activation and NF-κB-mediated cytokine production.Immunology and cell biology · 2026Article
- Inhibition of LSD1 enhances T cells anti-tumor immunity by promoting TNFSF14 expression in gastric cancer.Molecular and cellular biochemistry · 2026Article
- CD4/CD8-p56Biomolecules · 2025Review
- Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma.Scientific reports · 2025Article
- FYB1-targeted modulation of CAPG promotes AML progression.Molecular and cellular biochemistry · 2025Article
- T cells in ARAP-deficient mice present defective T cell receptor signaling and reduced severity in an experimentally-induced autoimmune disease.Frontiers in immunology · 2025Article
- The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events.Frontiers in immunology · 2021Review
- MAPK10 Expression as a Prognostic Marker of the Immunosuppressive Tumor Microenvironment in Human Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- How the Discovery of the CD4/CD8-p56Frontiers in cell and developmental biology · 2021Review
- The DISC1-Girdin complex - a missing link in signaling to the T cell cytoskeleton.Journal of cell science · 2020Article
- Immune adaptor SKAP1 acts a scaffold for Polo-like kinase 1 (PLK1) for the optimal cell cycling of T-cells.Scientific reports · 2019Article
- Crk adaptor proteins mediate actin-dependent T cell migration and mechanosensing induced by the integrin LFA-1.Science signaling · 2018Article
- ADAP is an upstream regulator that precedes SLP-76 at sites of TCR engagement and stabilizes signaling microclusters.Journal of cell science · 2018Article
- Integrins Modulate T Cell Receptor Signaling by Constraining Actin Flow at the Immunological Synapse.Frontiers in immunology · 2018Article
- The Role of Mst1 in Lymphocyte Homeostasis and Function.Frontiers in immunology · 2018Review
- G-CSF inhibits LFA-1-mediated CD4Oncotarget · 2017Article
- LFA-1 activates focal adhesion kinases FAK1/PYK2 to generate LAT-GRB2-SKAP1 complexes that terminate T-cell conjugate formation.Nature communications · 2017Article
- Activated Cdc42-associated kinase 1 (ACK1) binds the sterile α motif (SAM) domain of the adaptor SLP-76 and phosphorylates proximal tyrosines.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Although adaptor ADAP (FYB) and its binding to SLP-76 has been implicated in TcR-induced "inside-out" signaling for LFA-1 activation in T cells, little is known regarding its role in LFA-1-mediated "outside-in" signaling. In this study, we demonstrate that ADAP and SLP-76-ADAP binding are coupled to LFA-1 costimulation of IL-2 production, F-actin clustering, cell polarization, and T cell motility. LFA-1 enhancement of anti-CD3-induced IL-2 production was completely dependent on SLP-76-ADAP binding. Further, anti-CD3 was found to require CD11a ligation by antibody or ICAM1 to cause T cell polarization. ADAP augmented this polarization induced by anti-CD3/CD11a, but not by anti-CD3 alone. ADAP expression with LFA-1 ligation alone was sufficient to polarize T cells directly and to increase T cell motility whereas the loss of ADAP in ADAP-/- primary T cells reduced motility. A mutant lacking SLP-76-binding sites (M12) blocked LFA-1 costimulation of IL-2 production, polarization, and motility. LFA-1-ADAP polarization was also dependent on src kinases, Rho GTPases, phospholipase C, and phosphoinositol 3-kinase. Our findings provide evidence of an obligatory role for the SLP-76-ADAP module in LFA-1-mediated costimulation in T cells.
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