ArticleMolecular and cellular biology2006
Lck SH3 domain function is required for T-cell receptor signals regulating thymocyte development.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Type of PaperY192 within the SH2 Domain of Lck Regulates TCR Signaling Downstream of PLC-γ1 and Thymic Selection.International journal of molecular sciences · 2022Article
- ZAP70, too little, too much can lead to autoimmunity.Immunological reviews · 2022Review
- Adapting T Cell Receptor Ligand Discrimination CapabilityFrontiers in immunology · 2021Review
- Noncanonical binding of Lck to CD3ε promotes TCR signaling and CAR function.Nature immunology · 2020Article
- Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT.Nature immunology · 2018Article
- A PLC-γ1 Feedback Pathway Regulates Lck Substrate Phosphorylation at the T-Cell Receptor and SLP-76 Complex.Journal of proteome research · 2017Article
- Article
- Lck, Membrane Microdomains, and TCR Triggering Machinery: Defining the New Rules of Engagement.Frontiers in immunology · 2012Article
- Gene expression alterations in immune system pathways in the thymus after exposure to immunosuppressive chemicals.Environmental health perspectives · 2011Article
- Selective regulation of TCR signaling pathways by the CD45 protein tyrosine phosphatase during thymocyte development.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- The SH3 domain of Lck modulates T-cell receptor-dependent activation of extracellular signal-regulated kinase through activation of Raf-1.Molecular and cellular biology · 2008Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Thymocyte development is shaped by signals from the T-cell antigen receptor. The strength of receptor signaling determines developmental progression as well as deletion of self-reactive T cells. Receptor stimulation of the extracellular signal-regulated kinase (ERK) pathway plays an important regulatory role during thymocyte development. However, it is unclear how differences in receptor signaling are translated into distinctive activation of the ERK pathway. We have investigated the potential role of the Lck tyrosine kinase in regulating intracellular signaling during thymocyte development. While Lck is known to be critical for initial T-cell receptor signaling events, it may have an independent role in regulating intracellular signaling through the function of its SH3 domain. To determine whether such a regulatory mechanism functions during thymocyte development, we generated mice in which the normal lck allele is replaced with an lck SH3 domain mutant. Analysis of these mice revealed that both early thymocyte development and maturation of CD4(+) and CD8(+) lineages is impaired. Investigation of thymocyte responses to antigen receptor stimulation showed a significant reduction in proliferation and ERK pathway activation, although initial signaling events were intact. These findings indicate that Lck SH3 domain function may provide a means to independently couple receptor signaling to regulation of the ERK pathway during thymocyte development.
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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.