ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Nck recruitment to the TCR required for ZAP70 activation during thymic development.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomised, Double-blind, Placebo-controlled, Study of the Safety, Tolerability, and Pharmacokinetics of AX-158 Following Administration of Single and, Multiple Ascending Oral Doses and Food Effect Sub-study in Healthy Male Volunteers
A Phase 2a, Proof of Concept Study Evaluating the Safety and Tolerability of AX-158 in Patients With Mild to Moderate Plaque Psoriasis
Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- From TCR fundamental research to innovative chimeric antigen receptor design.Nature reviews. Immunology · 2025Review
- Nck1 regulates the in vitro development of human regulatory T cells through AKT pathway.Clinical and experimental immunology · 2025Article
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mutation of the Polyproline Sequence in CD3ε Evidences TCR Signaling Requirements for Differentiation and Function of Pro-Inflammatory Tγδ17 Cells.Frontiers in immunology · 2022Article
- Article
- Noncanonical binding of Lck to CD3ε promotes TCR signaling and CAR function.Nature immunology · 2020Article
- RRAS2 shapes the TCR repertoire by setting the threshold for negative selection.The Journal of experimental medicine · 2019Article
- Anti-CD3 Fab Fragments Enhance Tumor Killing by Human γδ T Cells Independent of Nck Recruitment to the γδ T Cell Antigen Receptor.Frontiers in immunology · 2018Article
- Review
- Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants.Oncotarget · 2016Article
- Action and Traction: Cytoskeletal Control of Receptor Triggering at the Immunological Synapse.Frontiers in immunology · 2016Review
- T cell specific adaptor protein (TSAd) promotes interaction of Nck with Lck and SLP-76 in T cells.Cell communication and signaling : CCS · 2015Article
- Ncking BCR-mediated PI3K activation.EMBO reports · 2013Article
- Multimolecular analysis of stable immunological synapses reveals sustained recruitment and sequential assembly of signaling clusters.Molecular & cellular proteomics : MCP · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adaptor protein Nck is inducibly recruited through its SH3.1 domain to a proline-rich sequence (PRS) in CD3ε after TCR engagement. However, experiments with a knockin mutant bearing an 8-aa replacement of the PRS have indicated that Nck binding to the TCR is constitutive, and that it promotes the degradation of the TCR in preselection double-positive (DP) CD4(+)CD8(+) thymocytes. To clarify these discrepancies, we have generated a new knockin mouse line (KI-PRS) bearing a conservative mutation in the PRS resulting from the replacement of the two central prolines. Thymocytes of KI-PRS mice are partly arrested at each step at which pre-TCR or TCR signaling is required. The mutation prevents the trigger-dependent inducible recruitment of endogenous Nck to the TCR but does not impair TCR degradation. However, KI-PRS preselection DP thymocytes show impaired tyrosine phosphorylation of CD3ζ, as well as impaired recruitment of ZAP70 to the TCR and impaired ZAP70 activation. Our results indicate that Nck is recruited to the TCR in an inducible manner in DP thymocytes, and that this recruitment is required for the activation of early TCR-dependent events. Differences in the extent of PRS mutation could explain the phenotypic differences in both knockin mice.
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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.