ArticleProceedings of the National Academy of Sciences of the United States of America2001
Ubiquitination and degradation of Syk and ZAP-70 protein tyrosine kinases in human NK cells upon CD16 engagement.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 57 citations in OpenAlex.
- FTO promotes human NK cell proliferation yet restricts effector functions.Acta pharmacologica Sinica · 2026Article
- The Ubiquitin-Proteasome System: A Key Regulatory Hub in Myocarditis Leading to Dilated Cardiomyopathy.Journal of inflammation research · 2025Review
- Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance.Cancers · 2024Review
- From CD16a Biology to Antibody-Dependent Cell-Mediated Cytotoxicity Improvement.Frontiers in immunology · 2022Review
- Immunomodulatory drugs activate NK cells via both Zap-70 and cereblon-dependent pathways.Leukemia · 2021Article
- Inhibition of the deubiquitinase USP10 induces degradation of SYK.British journal of cancer · 2020Article
- Post-translational Mechanisms Regulating NK Cell Activating Receptors and Their Ligands in Cancer: Potential Targets for Therapeutic Intervention.Frontiers in immunology · 2019Review
- Human NK Cells Downregulate Zap70 and Syk in Response to Prolonged Activation or DNA Damage.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Strategies to enhance NK cell function for the treatment of tumors and infections.Critical reviews in immunology · 2018Review
- Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS.PLoS pathogens · 2017Article
- Evaluation of the Functional Capacity of NK Cells of Melanoma Patients in an In Vitro Model of NK Cell Contact with K562 and FemX Tumor Cell Lines.The Journal of membrane biology · 2017Article
- Regulation of NKG2D-Dependent NK Cell Functions: The Yin and the Yang of Receptor Endocytosis.International journal of molecular sciences · 2017Review
- Article
- Non-degradative Ubiquitination of Protein Kinases.PLoS computational biology · 2016Article
- Cbl ubiquitin ligases mediate the inhibition of natural killer cell activity.Communicative & integrative biology · 2016Article
- K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8(+) T cell activation.Nature immunology · 2015Article
- Regulation of fc receptor endocytic trafficking by ubiquitination.Frontiers in immunology · 2014Review
- β2 integrin induces TCRζ-Syk-phospholipase C-γ phosphorylation and paxillin-dependent granule polarization in human NK cells.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Syk and pTyr'd: Signaling through the B cell antigen receptor.Biochimica et biophysica acta · 2009Review
- Up on the tightrope: natural killer cell activation and inhibition.Nature immunology · 2008Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Syk and ZAP-70 nonreceptor protein tyrosine kinases (PTKs) are essential elements in several cascades coupling immune receptors to intracellular responses. The critical role of these kinases in promoting the propagation of intracellular signaling requires a tight regulation of their activity, thus the existence of a negative feedback loop regulating their expression can be hypothesized. Herein, we have investigated whether ubiquitin-dependent proteolysis could be a mechanism responsible for controlling the fate of Syk and ZAP-70 after their immunoreceptor-induced activation. We found that both Syk and ZAP-70 become ubiquitinated in response to aggregation of the low affinity Fc receptor for IgG (CD16) on human natural killer cells. We confirmed the identity of the major in vivo ubiquitinated kinase species by performing an in vitro ubiquitination assay. In addition, we found that after CD16 stimulation, ubiquitinated forms of Syk and ZAP-70 associate with the receptor complex. After CD16 engagement, we also observed a decrease in the stability of Syk and ZAP-70 PTKs that is counteracted by pretreatment with either proteasome or lysosomal inhibitors. Moreover, in the presence of the proteasome inhibitor, epoxomicin, we observed an accumulation of ubiquitinated forms of both kinases. Our findings provide evidence of ligand-induced ubiquitination of nonreceptor PTKs belonging to the Syk family and propose the ubiquitin-dependent proteasome-mediated degradation pathway as a mechanism for attenuating the propagation of intracellular signaling initiated by immune receptor engagement.
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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.