ArticleJournal of immunology (Baltimore, Md. : 1950)2011
β2 integrin induces TCRζ-Syk-phospholipase C-γ phosphorylation and paxillin-dependent granule polarization in human NK cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- The membrane distal domain of CD16a allosterically regulates NK cell ADCC.bioRxiv : the preprint server for biology · 2026Article
- CAR-mediated targeting of NK cells overcomes tumor immune escape caused by ICAM-1 downregulation.Journal for immunotherapy of cancer · 2024Article
- Review
- The Interplay between Integrins and Immune Cells as a Regulator in Cancer Immunology.International journal of molecular sciences · 2023Review
- Review
- The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function.Frontiers in cell and developmental biology · 2021Review
- β2 Integrins-Multi-Functional Leukocyte Receptors in Health and Disease.International journal of molecular sciences · 2020Review
- PD-1 blocks lytic granule polarization with concomitant impairment of integrin outside-in signaling in the natural killer cell immunological synapse.The Journal of allergy and clinical immunology · 2018Article
- Review
- Integrins Modulate T Cell Receptor Signaling by Constraining Actin Flow at the Immunological Synapse.Frontiers in immunology · 2018Article
- Impact of Mixed Xenogeneic Porcine Hematopoietic Chimerism on Human NK Cell Recognition in a Humanized Mouse Model.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
- Origins of the cytolytic synapse.Nature reviews. Immunology · 2016Review
- Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients.Gene regulation and systems biology · 2016Article
- CD11c/CD18 Signals Very Late Antigen-4 Activation To Initiate Foamy Monocyte Recruitment during the Onset of Hypercholesterolemia.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Integrins Influence the Size and Dynamics of Signaling Microclusters in a Pyk2-dependent Manner.The Journal of biological chemistry · 2015Article
- F-actin flow drives affinity maturation and spatial organization of LFA-1 at the immunological synapse.The Journal of cell biology · 2015Article
- A signaling network stimulated by β2 integrin promotes the polarization of lytic granules in cytotoxic cells.Science signaling · 2014Article
- Distinct structural and catalytic roles for Zap70 in formation of the immunological synapse in CTL.eLife · 2014Article
- Activation of Lymphocyte Cytolytic Machinery: Where are We?Frontiers in immunology · 2013Review
- Cutting edge: NK cell licensing modulates adhesion to target cells.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Cytotoxic lymphocytes kill target cells through polarized release of the content of lytic granules at the immunological synapse. In human NK cells, signals for granule polarization and for degranulation can be uncoupled: Binding of β(2) integrin LFA-1 to ICAM is sufficient to induce polarization but not degranulation, whereas CD16 binding to IgG triggers unpolarized degranulation. In this study, we investigated the basis for this difference. IL-2-expanded human NK cells were stimulated by incubation with plate-bound ligands of LFA-1 (ICAM-1) and CD16 (human IgG). Surprisingly, LFA-1 elicited signals similar to those induced by CD16, including tyrosine phosphorylation of the TCR ζ-chain, tyrosine kinase Syk, and phospholipase C-γ. Whereas CD16 activated Ca(2+) mobilization and LAT phosphorylation, LFA-1 did not, but induced strong Pyk2 and paxillin phosphorylation. LFA-1-dependent granule polarization was blocked by inhibition of Syk, phospholipase C-γ, and protein kinase C, as well as by paxillin knockdown. Therefore, common signals triggered by CD16 and LFA-1 bifurcate to provide independent control of Ca(2+)-dependent degranulation and paxillin-dependent granule polarization.
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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.