ArticleThe Journal of cell biology2000
The tyrosine kinase PYK-2/RAFTK regulates natural killer (NK) cell cytotoxic response, and is translocated and activated upon specific target cell recognition and killing.
Article in The Journal of cell biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 89 citations in OpenAlex.
- Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells.Journal of leukocyte biology · 2015Trial
- CD33Journal for immunotherapy of cancer · 2025Article
- Targeting the hydrophobic pockets of FAK/PYK2 FAT domain: a highly effective inhibitory strategy suppressing tumor growth and eliminating metastasis.Cell communication and signaling : CCS · 2025Article
- CD56/NCAM mediates cell migration of human NK cells by promoting integrin-mediated adhesion turnover.Molecular biology of the cell · 2024Article
- CD56/NCAM mediates cell migration of human NK cells by promoting integrin-mediated adhesion turnover.bioRxiv : the preprint server for biology · 2023Article
- 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
- Article
- JAK/STAT Cytokine Signaling at the Crossroad of NK Cell Development and Maturation.Frontiers in immunology · 2019Review
- Genetic determinants and an epistasis ofProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Micro-adhesion rings surrounding TCR microclusters are essential for T cell activation.The Journal of experimental medicine · 2016Article
- Origins of the cytolytic synapse.Nature reviews. Immunology · 2016Review
- A signaling network stimulated by β2 integrin promotes the polarization of lytic granules in cytotoxic cells.Science signaling · 2014Article
- Functions of the FAK family kinases in T cells: beyond actin cytoskeletal rearrangement.Immunologic research · 2014Review
- Cell biological steps and checkpoints in accessing NK cell cytotoxicity.Immunology and cell biology · 2014Review
- Human immunodeficiency syndromes affecting human natural killer cell cytolytic activity.Frontiers in immunology · 2014Review
- Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell-mediated cytotoxicity.Molecular biology of the cell · 2013Article
- Activation of Lymphocyte Cytolytic Machinery: Where are We?Frontiers in immunology · 2013Review
- Controlling natural killer cell responses: integration of signals for activation and inhibition.Annual review of immunology · 2013Review
- Human NK cell lytic granules and regulation of their exocytosis.Frontiers in immunology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The compartmentalization of plasma membrane proteins has a key role in regulation of lymphocyte activation and development of immunity. We found that the proline-rich tyrosine kinase-2 (PYK-2/RAFTK) colocalized with the microtubule-organizing center (MTOC) at the trailing edge of migrating natural killer (NK) cells. When polyclonal NK cells bound to K562 targets, PYK-2 translocated to the area of NK-target cell interaction. The specificity of this process was assessed with NK cell clones bearing activatory or inhibitory forms of CD94/NKG2. The translocation of PYK-2, MTOC, and paxillin to the area of NK-target cell contact was regulated upon specific recognition of target cells through NK cell receptors, controlling target cell killing. Furthermore, parallel in vitro kinase assays showed that PYK-2 was activated in response to signals that specifically triggered its translocation and NK cell mediated cytotoxicity. The overexpression of both the wt and a dominant-negative mutant of PYK-2, but not ZAP-70 wt, prevented the specific translocation of the MTOC and paxillin, and blocked the cytotoxic response of NK cells. Our data indicate that subcellular compartmentalization of PYK-2 correlates with effective signal transduction. Furthermore, they also suggest an important role for PYK-2 on the assembly of the signaling complexes that regulate the cytotoxic response.
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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.