ArticleScience signaling2014
A signaling network stimulated by β2 integrin promotes the polarization of lytic granules in cytotoxic cells.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
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- CAR-mediated targeting of NK cells overcomes tumor immune escape caused by ICAM-1 downregulation.Journal for immunotherapy of cancer · 2024Article
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- LFA-1/ ICAM-1 promotes NK cell cytotoxicity associated with the pathogenesis of ocular toxoplasmosis in murine model.PLoS neglected tropical diseases · 2022Article
- Spatially resolved in silico modeling of NKG2D signaling kinetics suggests a key role of NKG2D and Vav1 Co-clustering in generating natural killer cell activation.PLoS computational biology · 2022Article
- C3aR Signaling Inhibits NK-cell Infiltration into the Tumor Microenvironment in Mouse Models.Cancer immunology research · 2022Article
- β2-Integrins - Regulatory and Executive Bridges in the Signaling Network Controlling Leukocyte Trafficking and Migration.Frontiers in immunology · 2022Review
- Cathepsin X Activity Does Not Affect NK-Target Cell Synapse but Is Rather Distributed to Cytotoxic Granules.International journal of molecular sciences · 2021Article
- Cereblon regulates NK cell cytotoxicity and migration via Rac1 activation.European journal of immunology · 2021Article
- Natural killer cells in pancreatic cancer stroma.World journal of gastroenterology · 2021Review
- Inability of granule polarization by NK cells defines tumor resistance and can be overcome by CAR or ADCC mediated targeting.Journal for immunotherapy of cancer · 2021Article
- Dynamic Microtubule Arrays in Leukocytes and Their Role in Cell Migration and Immune Synapse Formation.Frontiers in cell and developmental biology · 2021Review
- 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
- Article
- Review
- β2 Integrins-Multi-Functional Leukocyte Receptors in Health and Disease.International journal of molecular sciences · 2020Review
- NKG2D-DAP10 signaling recruits EVL to the cytotoxic synapse to generate F-actin and promote NK cell cytotoxicity.Journal of cell science · 2019Article
- VASP Regulates NK Cell Lytic Granule Convergence.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- 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
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4 authors at 2 institutions in 1 country.
Funding
Abstract
Cytotoxic lymphocytes kill target cells through the polarized release of the contents of intracellular perforin-containing granules. In natural killer (NK) cells, the binding of β2 integrin to members of the intercellular adhesion molecule family is sufficient to promote not only the adhesion of NK cells to target cells but also the polarization of intracellular lytic granules toward the target. We used NK cells in an experimental system designed to enable us to study the polarization of lytic granules in the absence of their release through degranulation, as well as β2 integrin signaling independently of inside-out signals from other receptors. Through a proteomics approach, we identified a signaling network centered on an integrin-linked kinase (ILK)-Pyk2-paxillin core that was required for granule and microtubule-organizing center (MTOC) polarization. The conserved Cdc42-Par6 signaling pathway, which controls cell polarity, was also activated by ILK and was required for granule polarization toward the target cell. A subset of the signaling components required for polarization contributed also to the convergence of granules on the MTOC. These results delineate two connected signaling networks that are stimulated upon β2 integrin engagement and control the polarization of the MTOC and associated lytic granules toward the site of contact with target cells to mediate cellular cytotoxicity.
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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.