ArticleCell communication and signaling : CCS2014
Non-overlapping functions of Nck1 and Nck2 adaptor proteins in T cell activation.
Article in Cell communication and signaling : CCS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- The Y105 phosphosite between the SH3.1 and SH3.2 domains of Nck1 regulates its binding to CD3ϵ.iScience · 2026Article
- Regulation of trophoblast fusion dysfunction in preeclampsia by the NCK1/EIF3D/PPARG axis.Biological research · 2026Article
- Nck1 regulates the in vitro development of human regulatory T cells through AKT pathway.Clinical and experimental immunology · 2025Article
- Lack of Nck1 protein and Nck-CD3 interaction caused the increment of lipid content in Jurkat T cells.BMC molecular and cell biology · 2022Article
- Essential function of adaptor protein Nck1 in platelet-derived growth factor receptor signaling in human lens epithelial cells.Scientific reports · 2022Article
- Precise levels of the Drosophila adaptor protein Dreadlocks maintain the size and stability of germline ring canals.Journal of cell science · 2021Article
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- Sinner or Saint?: Nck Adaptor Proteins in Vascular Biology.Frontiers in cell and developmental biology · 2021Review
- A sensitive S-Trap-based approach to the analysis of T cell lipid raft proteome.Journal of lipid research · 2020Article
- Selective role of Nck1 in atherogenic inflammation and plaque formation.The Journal of clinical investigation · 2020Article
- Nck1 promotes the progression of ovarian carcinoma by enhancing the PI3K/AKT/p70S6K signaling.Human cell · 2020Article
- Small molecule AX-024 reduces T cell proliferation independently of CD3ϵ/Nck1 interaction, which is governed by a domain swap in the Nck1-SH3.1 domain.The Journal of biological chemistry · 2020Article
- Nck1, But Not Nck2, Mediates Disturbed Flow-Induced p21-Activated Kinase Activation and Endothelial Permeability.Journal of the American Heart Association · 2020Article
- Actin polymerization regulates recruitment of Nck to CD3ε upon T-cell receptor triggering.Immunology · 2020Article
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- Article
- Review
- Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci.Scientific reports · 2017Article
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
backgroundSignalling by the T cell antigen receptor (TCR) results in the activation of T lymphocytes. Nck1 and Nck2 are two highly related adaptor proteins downstream of the TCR that each contains three SH3 and one SH2 domains. Their individual functions and the roles of their SH3 domains in human T cells remain mostly unknown.
resultsUsing specific shRNA we down-regulated the expression of Nck1 or Nck2 to approximately 10% each in Jurkat T cells. We found that down-regulation of Nck1 impaired TCR-induced phosphorylation of the kinases Erk and MEK, activation of the AP-1 and NFAT transcription factors and subsequently, IL-2 and CD69 expression. In sharp contrast, down-regulation of Nck2 hardly impacts these activation read-outs. Thus, in contrast to Nck2, Nck1 is a positive regulator for TCR-induced stimulation of the Erk pathway. Mutation of the third SH3 domain of Nck1 showed that this domain was required for this activity. Further, TCR-induced NFAT activity was reduced in both Nck1 and Nck2 knock-down cells, showing that both isoforms are involved in NFAT activation. Lastly, we show that neither Nck isoform is upstream of p38 phosphorylation or Ca2+influx.
conclusionsIn conclusion, Nck1 and Nck2 have non-redundant roles in human T cell activation in contrast to murine T cells.
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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.