ArticleImmunology and cell biology2015
The pool of preactivated Lck in the initiation of T-cell signaling: a critical re-evaluation of the Lck standby model.
Article in Immunology and cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 36 citations in OpenAlex.
- Spatial regulation of Lck activation at the CD8 immune synapse revealed by a FRET-Based biosensor.Cellular and molecular life sciences : CMLS · 2026Article
- CD147 regulates CD8iScience · 2026Article
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- Mechanical forces amplify TCR mechanotransduction in T cell activation and function.Applied physics reviews · 2024Review
- 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
- The kinase occupancy of T cell coreceptors reconsidered.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Regulating the discriminatory response to antigen by T-cell receptor.Bioscience reports · 2022Review
- Characterization of a library of 20 HBV-specific MHC class II-restricted T cell receptors.Molecular therapy. Methods & clinical development · 2021Article
- Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein.European journal of immunology · 2021Article
- TCR-T Immunotherapy: The Challenges and Solutions.Frontiers in oncology · 2021Review
- Noncanonical binding of Lck to CD3ε promotes TCR signaling and CAR function.Nature immunology · 2020Article
- Lck bound to coreceptor is less active than free Lck.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Spatiotemporal Regulation of Signaling: Focus on T Cell Activation and the Immunological Synapse.International journal of molecular sciences · 2020Review
- Conformational States Control Lck Switching between Free and Confined Diffusion Modes in T Cells.Biophysical journal · 2020Article
- Structural understanding of T cell receptor triggering.Cellular & molecular immunology · 2020Review
- Biophysical basis underlying dynamic Lck activation visualized by ZapLck FRET biosensor.Science advances · 2019Article
- Dual Role of CD4 in Peripheral T Lymphocytes.Frontiers in immunology · 2019Review
- The Ciliary Machinery Is Repurposed for T Cell Immune Synapse Trafficking of LCK.Developmental cell · 2018Article
- Regulatory mechanisms in T cell receptor signalling.Nature reviews. Immunology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The initiation of T-cell receptor (TCR) signaling, based on the cobinding of TCR and CD4-Lck heterodimer to a peptide-major histocompatibility complex II on antigen presenting cells, represents a classical model of T-cell signaling. What is less clear however, is the mechanism which translates TCR engagement to the phosphorylation of immunoreceptor tyrosine-based activation motifs on CD3 chains and how this event is coupled to the delivery of Lck function. Recently proposed 'standby model of Lck' posits that resting T-cells contain an abundant pool of constitutively active Lck (pY394(Lck)) required for TCR triggering, and this amount, upon TCR engagement, remains constant. Here, we show that although maintenance of the limited pool of pY394(Lck) is necessary for the generation of TCR proximal signals in a time-restricted fashion, the total amount of this pool, ~2%, is much smaller than previously reported (~40%). We provide evidence that this dramatic discrepancy in the content of pY394(Lck)is likely the consequence of spontaneous phosphorylation of Lck that occurred after cell solubilization. Additional discrepancies can be accounted for by the sensitivity of different pY394(Lck)-specific antibodies and the type of detergents used. These data suggest that reagents and conditions used for the quantification of signaling parameters must be carefully validated and interpreted. Thus, the limited size of pY394(Lck) pool in primary T-cells invites a discussion regarding the adjustment of the quantitative parameters of the standby model of Lck and reevaluation of the mechanism by which this pool contributes to the generation of proximal 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.