ArticleThe Journal of experimental medicine1999
Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulation.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 181 citations in OpenAlex.
- A motif-vocabulary model of CAR T-cell intracellular domains identifies determinants of immunophenotype differentiation.bioRxiv : the preprint server for biology · 2026Article
- The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- A CD8αβ co-receptor modified to contain an intracellular CD28 signaling tail enhances TCR-engineered T cell function independent of solid-tumor-associated co-stimulatory ligands.Nature communications · 2026Article
- Advances in CAR optimization strategies based on CD28.Frontiers in immunology · 2025Review
- CD28 Costimulation Augments CAR Signaling in NK Cells via the LCK/CD3ζ/ZAP70 Signaling Axis.Cancer discovery · 2024Article
- Costimulatory receptors in the channel catfish: CD28 family members and their ligands.Immunogenetics · 2024Article
- CD28 and chemokine receptors: Signalling amplifiers at the immunological synapse.Frontiers in immunology · 2022Review
- Review
- [Structural optimization and prospect of chimeric antigen receptor T cells].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Article
- Article
- CD28 Costimulatory Domain-Targeted Mutations Enhance Chimeric Antigen Receptor T-cell Function.Cancer immunology research · 2021Article
- Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability.The Journal of clinical investigation · 2020Article
- THEMIS-SHP1 Recruitment by 4-1BB Tunes LCK-Mediated Priming of Chimeric Antigen Receptor-Redirected T Cells.Cancer cell · 2020Article
- Computational Model of Chimeric Antigen Receptors Explains Site-Specific Phosphorylation Kinetics.Biophysical journal · 2018Article
- Low level of Lck kinase in Th2 cells limits expression of CD4 co-receptor and S73 phosphorylation of transcription factor c-Jun.Scientific reports · 2017Article
- Membrane Rafts in T Cell Activation: A Spotlight on CD28 Costimulation.Frontiers in immunology · 2017Review
- Binding of the cytoplasmic domain of CD28 to the plasma membrane inhibits Lck recruitment and signaling.Science signaling · 2016Article
- CD28 Costimulation: From Mechanism to Therapy.Immunity · 2016Review
- Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition.Frontiers in immunology · 2016Review
- Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling.Nature immunology · 2014Article
2 more citing papers are in PubMed but not listed here.
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 4 institutions in 1 country.
Funding
Abstract
The Src family tyrosine kinases Lck and Fyn are critical for signaling via the T cell receptor. However, the exact mechanism of their activation is unknown. Recent crystal structures of Src kinases suggest that an important mechanism of kinase activation is via engagement of the Src homology (SH)3 domain by proline-containing sequences. To test this hypothesis, we identified several T cell membrane proteins that contain potential SH3 ligands. Here we demonstrate that Lck and Fyn can be activated by proline motifs in the CD28 and CD2 proteins, respectively. Supporting a role for Lck in CD28 signaling, we demonstrate that CD28 signaling in both transformed and primary T cells requires Lck as well as proline residues in CD28. These data suggest that Lck plays an essential role in CD28 costimulation.
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.