ArticleCell reports2016
The Csk-Associated Adaptor PAG Inhibits Effector T Cell Activation in Cooperation with Phosphatase PTPN22 and Dok Adaptors.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- CD200R1-CD200 checkpoint inhibits phagocytosis differently from SIRPα-CD47 to suppress tumor growth.Nature communications · 2025Article
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- miR-143-3p Promotes TGenes · 2025Article
- DOK1 and DOK2 regulate CD8 T cell signaling and memory formation without affecting tumor cell killing.Scientific reports · 2024Article
- Regulation of T Cell Signaling and Immune Responses by PTPN22.Molecular and cellular biology · 2024Review
- Immunotherapeutic implications of negative regulation by protein tyrosine phosphatases in T cells: the emerging cases of PTP1B and TCPTP.Frontiers in medicine · 2024Review
- CD47 masks pro-phagocytic ligands in cis on tumor cells to suppress antitumor immunity.Nature immunology · 2023Article
- A Story of Kinases and Adaptors: The Role of Lck, ZAP-70 and LAT in Switch Panel Governing T-Cell Development and Activation.Biology · 2023Review
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- Article
- Regulation, targets and functions of CSK.Frontiers in cell and developmental biology · 2023Review
- Redox regulation of PTPN22 affects the severity of T-cell-dependent autoimmune inflammation.eLife · 2022Article
- Inherited immunodeficiencies associated with proximal and distal defects in T cell receptor signaling and co-signaling.Biomedical journal · 2022Review
- Combination Approaches to Target PD-1 Signaling in Cancer.Frontiers in immunology · 2022Review
- Regulation of T cell function by protein S-acylation.Frontiers in physiology · 2022Review
- Acute Csk inhibition hinders B cell activation by constraining the PI3 kinase pathway.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Overexpression of theJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- The TIM3/Gal9 signaling pathway: An emerging target for cancer immunotherapy.Cancer letters · 2021Article
- TRAF3 in T Cells Restrains Negative Regulators of LAT to Promote TCR/CD28 Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
The transmembrane adaptor PAG (Cbp) has been proposed to mediate membrane recruitment of Csk, a cytoplasmic protein tyrosine kinase playing a critical inhibitory role during T cell activation, by inactivating membrane-associated Src kinases. However, this model has not been validated by genetic evidence. Here, we demonstrate that PAG-deficient mice display enhanced T cell activation responses in effector, but not in naive, T cells. PAG-deficient mice also have augmented T cell-dependent autoimmunity and greater resistance to T cell anergy. Interestingly, in the absence of PAG, Csk becomes more associated with alternative partners; i.e., phosphatase PTPN22 and Dok adaptors. Combining PAG deficiency with PTPN22 or Dok adaptor deficiency further enhances effector T cell responses. Unlike PAG, Cbl ubiquitin ligases inhibit the activation of naive, but not of effector, T cells. Thus, Csk-associating PAG is a critical component of the inhibitory machinery controlling effector T cell activation in cooperation with PTPN22 and Dok adaptors.
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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.