ArticleThe Journal of experimental medicine2006
T cell receptor for antigen induces linker for activation of T cell-dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2.
Article in The Journal of experimental medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 119 citations in OpenAlex.
- KLRG1 silencing increases the efficacy of CAR NK cell therapy against colon cancer via SHP-2/ZAP-70/NF-κB signal pathway.Journal of translational medicine · 2026Article
- PTPN11 in cartilage development, adult homeostasis, and diseases.Bone research · 2025Review
- Imaging of biphasic signalosomes constructed by checkpoint receptor 2B4 in conventional and chimeric antigen receptor-T cells.iScience · 2025Article
- SHIP-1 regulates the differentiation and function of Tregs via inhibiting mTORC1 activity.Cellular and molecular life sciences : CMLS · 2024Article
- DOK1 and DOK2 regulate CD8 T cell signaling and memory formation without affecting tumor cell killing.Scientific reports · 2024Article
- Immunotherapeutic implications of negative regulation by protein tyrosine phosphatases in T cells: the emerging cases of PTP1B and TCPTP.Frontiers in medicine · 2024Review
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
- Introduction to DOK2 and its potential role in cancer.Physiological research · 2021Review
- Inhibition of lipid phosphatase SHIP1 expands myeloid-derived suppressor cells and attenuates rheumatoid arthritis in mice.American journal of physiology. Cell physiology · 2021Article
- TRAF3 in T Cells Restrains Negative Regulators of LAT to Promote TCR/CD28 Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The Clinical Aspect of Adaptor Molecules in T Cell Signaling: Lessons Learnt From Inborn Errors of Immunity.Frontiers in immunology · 2021Review
- "Non-Essential" Proteins of HSV-1 with Essential Roles In Vivo: A Comprehensive Review.Viruses · 2020Review
- CD5 signalosome coordinates antagonist TCR signals to control the generation of Treg cells induced by foreign antigens.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Prognostic role of DOK family adapters in acute myeloid leukemia.Cancer gene therapy · 2019Article
- Genome-Wide CRISPR Screen Identifies Host Factors Required byFrontiers in cellular and infection microbiology · 2019Article
- Id3 Restricts γδ NKT Cell Expansion by Controlling Egr2 and c-Myc Activity.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Cutting Edge: Check Your Mice-A Point Mutation in theJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Role of SHIP1 in Invariant NKT Cell Development and Functions.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- The signaling symphony: T cell receptor tunes cytokine-mediated T cell differentiation.Journal of leukocyte biology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adaptor proteins positively or negatively regulate the T cell receptor for antigen (TCR) signaling cascade. We report that after TCR stimulation, the inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are involved in a multimolecular complex including the lipid phosphatase Src homology 2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP)-1 and Grb-2 which interacts with the membrane signaling scaffold linker for activation of T cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a critical role in shaping the immune response and as gatekeepers for T cell tolerance.
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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.