ArticleCold Spring Harbor symposia on quantitative biology2013
Novel tools to dissect the dynamic regulation of TCR signaling by the kinase Csk and the phosphatase CD45.
Article in Cold Spring Harbor symposia on quantitative biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Bispecific Antibodies in Glioblastoma: Mechanistic Advances, Delivery Innovations, and Translational Challenges in Overcoming Immune Escape.International journal of medical sciences · 2025Review
- Programmable DNA-augmented hydrogels for controlled activation of human lymphocytes.Nanomedicine : nanotechnology, biology, and medicine · 2021Article
- Strategies to Address Chimeric Antigen Receptor Tonic Signaling.Molecular cancer therapeutics · 2018Review
- Tonic Signals: Why Do Lymphocytes Bother?Trends in immunology · 2017Review
- Initiation of T cell signaling by CD45 segregation at 'close contacts'.Nature immunology · 2016Article
- The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway.Science signaling · 2015Article
- The role of T cell receptor signaling thresholds in guiding T cell fate decisions.Current opinion in immunology · 2015Review
- In vitro membrane reconstitution of the T-cell receptor proximal signaling network.Nature structural & molecular biology · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Although the biochemical events induced by T-cell receptor (TCR) triggering have been well studied, both the mediators and function of basal signaling in T cells remain poorly understood. Furthermore, the precise mechanisms by which MHC-peptide interaction with the TCR disrupt the basal equilibrium to induce downstream signaling are also unclear. Here we describe novel approaches to understand the basal state of T cells and the mechanisms of TCR triggering by perturbing regulation of the Src family kinases (SFKs). The SFKs are critical proximal mediators of TCR signaling that are in turn tightly regulated by the tyrosine kinase Csk and the receptor-like tyrosine phosphatase CD45. We have developed a small-molecule analog-sensitive allele of Csk and an allelic series of mice in which expression of CD45 is varied across a broad range. Our studies have unmasked contributions of Csk and CD45 to maintain the basal state of T cells and also suggest that dynamic regulation of Csk may be involved in TCR triggering.
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Registered trials
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