ArticleProceedings of the National Academy of Sciences of the United States of America2010
Nck adaptors are positive regulators of the size and sensitivity of the T-cell repertoire.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. 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 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
18 citing papers in PubMed, 29 citations in OpenAlex.
- The Ste20 kinase TAOK3 restrains Rac-driven cytoskeletal-mitochondrial coupling to preserve naive CD8Frontiers in immunology · 2026Article
- SLAMF7 (CD319) on activated CD8Cell death and differentiation · 2025Article
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- New Label-Free Biosensing for the Evaluation of the AX-024 Inhibitor: Case Study for the Development of New Drugs in Autoimmune Diseases.Sensors (Basel, Switzerland) · 2022Article
- Nck adaptors at a glance.Journal of cell science · 2021Article
- ShcA expression in podocytes is dispensable for glomerular development but its upregulation is associated with kidney disease.American journal of translational research · 2021Article
- 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
- Peptide-based sequestration of the adaptor protein Nck1 in pancreatic β cells enhances insulin biogenesis and protects against diabetogenic stresses.The Journal of biological chemistry · 2018Article
- Recruitment of the adaptor protein Nck to PECAM-1 couples oxidative stress to canonical NF-κB signaling and inflammation.Science signaling · 2015Article
- Non-overlapping functions of Nck1 and Nck2 adaptor proteins in T cell activation.Cell communication and signaling : CCS · 2014Article
- Ncking BCR-mediated PI3K activation.EMBO reports · 2013Article
- Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells.Nature immunology · 2013Article
- Nck recruitment to the TCR required for ZAP70 activation during thymic development.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Evolution of SH2 domains and phosphotyrosine signalling networks.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2012Review
- Essential role of the adaptor protein Nck1 in Jurkat T cell activation and function.Clinical and experimental immunology · 2012Article
- Dendritic cells enhance the antigen sensitivity of T cells.Frontiers in immunology · 2012Article
- Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells.Nature immunology · 2011Review
- Integration of signaling and cytoskeletal remodeling by Nck in directional cell migration.BioarchitectureReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 8 institutions in 5 countries.
Funding
Abstract
The size and sensitivity of the T-cell repertoire governs the effectiveness of immune responses against invading pathogens. Both are modulated by T-cell receptor (TCR) activity through molecular mechanisms, which remain unclear. Here, we provide genetic evidence that the SH2/SH3 domain containing proteins Nck lower the threshold of T-cell responsiveness. The hallmarks of Nck deletion were T-cell lymphopenia and hyporeactivity to TCR-mediated stimulation. In the absence of the Nck adaptors, peripheral T cells expressing a TCR with low avidity for self-antigens were strongly reduced, whereas an overall impairment of T-cell activation by weak antigenic stimulation was observed. Mechanistically, Nck deletion resulted in a significant decrease in calcium mobilization and ERK phosphorylation upon TCR engagement. Taken together, our findings unveil a crucial role for the Nck adaptors in shaping the T-cell repertoire to ensure maximal antigenic coverage and optimal T cell excitability.
Indexed as
Identifiers
What OpenQuestion holds
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.