ArticleNature immunology2014
Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling.
Article in Nature immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 100 citations in OpenAlex.
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- Crk mediates Csk-Hippo signaling independently of Yap tyrosine phosphorylation to induce cell extrusion.bioRxiv : the preprint server for biology · 2024Article
- 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
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- A dominant function of LynB kinase in preventing autoimmunity.Science advances · 2022Article
- SH3-domain mutations selectively disrupt Csk homodimerization or PTPN22 binding.Scientific reports · 2022Article
- Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.Cell research · 2021Article
- 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
- NKD2 mediates stimulation-dependent ORAI1 trafficking to augment CaCell reports · 2021Article
- The deubiquitinase CYLD controls protective immunity against helminth infection by regulation of Treg cell plasticity.The Journal of allergy and clinical immunology · 2021Article
- CD45 pre-exclusion from the tips of T cell microvilli prior to antigen recognition.Nature communications · 2021Article
- Function of γδ T cells in tumor immunology and their application to cancer therapy.Experimental & molecular medicine · 2021Review
- T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice.Scientific reports · 2020Article
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6 authors at 3 institutions in 1 country.
Funding
Abstract
Signaling via the T cell antigen receptor (TCR) is initiated by Src-family kinases (SFKs). To understand how the kinase Csk, a negative regulator of SFKs, controls the basal state and the initiation of TCR signaling, we generated mice that express a Csk variant sensitive to an analog of the common kinase inhibitor PP1 (Csk(AS)). Inhibition of Csk(AS) in thymocytes, without engagement of the TCR, induced potent activation of SFKs and proximal TCR signaling up to phospholipase C-γ1 (PLC-γ1). Unexpectedly, increases in inositol phosphates, intracellular calcium and phosphorylation of the kinase Erk were impaired. Altering the actin cytoskeleton pharmacologically or providing costimulation via CD28 'rescued' those defects. Thus, Csk has a critical role in preventing TCR signaling. However, our studies also revealed a requirement for actin remodeling, initiated by costimulation, for full TCR signaling.
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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.