ArticleMolecular and cellular biology2000
Differential T-cell antigen receptor signaling mediated by the Src family kinases Lck and Fyn.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 114 citations in OpenAlex.
- Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream.Journal of translational medicine · 2007Trial
- Selective 7‑Azaindole Modulators Targeting Fyn and GSK-3β for Dual-Target Neuromodulation.ACS medicinal chemistry letters · 2026Article
- CSF1R-CAR T cells induce CSF1R signaling and can promote target cell proliferation.Science signaling · 2025Article
- Analysis of Striped Bass (Morone saxatilis) and White Bass (M. chrysops) Splenic Transcriptome Following Streptococcus iniae Infection.Marine biotechnology (New York, N.Y.) · 2025Article
- Advances in targeting protein S-palmitoylation in tumor immunity and therapy.Frontiers in oncology · 2025Review
- Exploring BenzylethoxyAryl Urea Scaffolds for Multitarget Immunomodulation Therapies.International journal of molecular sciences · 2023Article
- CD28-CAR-T cell activation through FYN kinase signaling rather than LCK enhances therapeutic performance.Cell reports. Medicine · 2023Article
- The potential of Senolytics in transplantation.Mechanisms of ageing and development · 2021Review
- Separate signaling events control TCR downregulation and T cell activation in primary human T cells.Immunity, inflammation and disease · 2021Article
- Signaling from T cell receptors (TCRs) and chimeric antigen receptors (CARs) on T cells.Cellular & molecular immunology · 2020Review
- The Role of Co-stimulatory/Co-inhibitory Signals in Graft-vs.-Host Disease.Frontiers in immunology · 2018Review
- Encoding optical control in LCK kinase to quantitatively investigate its activity in live cells.Nature structural & molecular biology · 2017Article
- Article
- Multifunctional double-negative T cells in sooty mangabeys mediate T-helper functions irrespective of SIV infection.PLoS pathogens · 2013Article
- Double-negative T cells during HIV/SIV infections: potential pinch hitters in the T-cell lineup.Current opinion in HIV and AIDS · 2012Review
- Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells.PloS one · 2012Article
- Lck, Membrane Microdomains, and TCR Triggering Machinery: Defining the New Rules of Engagement.Frontiers in immunology · 2012Article
- A new pathway of CD5 glycoprotein-mediated T cell inhibition dependent on inhibitory phosphorylation of Fyn kinase.The Journal of biological chemistry · 2011Article
- Fyn binds to and phosphorylates T cell immunoglobulin and mucin domain-1 (Tim-1).Molecular immunology · 2011Article
- Centrosome docking at the immunological synapse is controlled by Lck signaling.The Journal of cell biology · 2011Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Src family tyrosine kinases play a key role in T-cell antigen receptor (TCR) signaling. They are responsible for the initial tyrosine phosphorylation of the receptor, leading to the recruitment of the ZAP-70 tyrosine kinase, as well as the subsequent phosphorylation and activation of ZAP-70. Molecular and genetic evidence indicates that both the Fyn and Lck members of the Src family can participate in TCR signal transduction; however, it is unclear to what extent they utilize the same signal transduction pathways and activate the same downstream events. We have addressed this issue by examining the ability of Fyn to mediate TCR signal transduction in an Lck-deficient T-cell line (JCaM1). Fyn was able to induce tyrosine phosphorylation of the TCR and recruitment of the ZAP-70 kinase, but the pattern of TCR phosphorylation was altered and activation of ZAP-70 was defective. Despite this, the SLP-76 adapter protein was inducibly tyrosine phosphorylated, and both the Ras-mitogen-activated protein kinase and the phosphatidylinositol 4, 5-biphosphate signaling pathways were activated. TCR stimulation of JCaM1/Fyn cells induced the expression of the CD69 activation marker and inhibited cell growth, but NFAT activation and the production of interleukin-2 were markedly reduced. These results indicate that Fyn mediates an alternative form of TCR signaling which is independent of ZAP-70 activation and generates a distinct cellular phenotype. Furthermore, these findings imply that the outcome of TCR signal transduction may be determined by which Src family kinase is used to initiate signaling.
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