Evidence map›Paper›PMID 41000640›Full record

ArticlebioRxiv : the preprint server for biology2025

Weak SLP-76-PLC-γ1 interaction in the LAT-nucleated multi-protein complex fine-tunes TCR signal strength to optimize T cell responsiveness.

Hidehiro Yamane, Junya Wada, Elizabeth N Stassenko, Natalie D Convertino, Mariah E Lee, Melanie S Vacchio, Wenmei Li, Udumbara M Rathnayake, Lakshmi Balagopalan, Raj Chari and 5 more

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In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Hidehiro YamaneLaboratory of Cellular and Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.ORCID 0009-0008-3282-2515
Junya WadaLaboratory of Cellular and Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.
Elizabeth N StassenkoLaboratory of Cellular and Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.
Natalie D ConvertinoLaboratory of Cellular and Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.
Mariah E LeeLaboratory of Cellular and Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.
Melanie S VacchioLaboratory of Integrative Cancer Immunology, CCR, NCI, NIH, Bethesda, MD, U.S.A.
Wenmei LiLaboratory of Cellular and Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.
Udumbara M RathnayakeLaboratory of Cellular and Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.
Lakshmi BalagopalanLaboratory of Cellular and Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.
Raj ChariGenome Modification Core, Laboratory of Animal Sciences Program (LASP), Frederick National Laboratory for Cancer Research (FNLCR), NCI, NIH, Frederick, MD, U.S.A.
Herbert HagenauMouse Modeling and Cryopreservation, LASP, FNLCR, NCI, NIH, Frederick, MD, U.S.A.
Parirokh AwasthiMouse Modeling and Cryopreservation, LASP, FNLCR, NCI, NIH, Frederick, MD, U.S.A.
Dorian B McGavernViral Immunology & Intravital Imaging Section, Neuroimmunology & Neurovirology Division, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, U.S.A.
Remy BosselutLaboratory of Integrative Cancer Immunology, CCR, NCI, NIH, Bethesda, MD, U.S.A.
Lawrence E SamelsonLaboratory of Cellular and Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, U.S.A.

Funding

Biochemical Basis of T Cell ActivationZIABC010304 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SAMELSON, LAWRENCE · 2009 to 2025
$36.3M
Intramural NIH HHS ZIA BC010304
6 · The paper itself

Abstract

Upon TCR engagement several protein tyrosine kinases are recruited and activated, and adapter proteins and enzymes are phosphorylated on tyrosine residues, leading to further events characterizing activated T cells. Phosphorylation of the LAT adapter protein enables binding of the enzyme PLC-γ1 and of a dimer of two additional adapter proteins Gads and SLP-76, forming a tetrameric structure. Within this heterotetramer there is a weak interaction between SLP-76 and PLC-γ1, and the relevant binding sites of SLP-76 and PLC-γ1 are highly conserved in vertebrates. To address the biological relevance of this weak interaction, we introduced a mutation in the SLP-76 that enhanced its affinity for PLC-γ1 and found that this mutation increased PLC-γ1 activity and altered thymocyte development and peripheral T cell responses due to enhanced TCR signal strength. The conserved weak SLP-76-PLC-γ1 interaction is critical for the controlled activation of PLC-γ1, thus fine-tuning TCR signal strength to optimize T cell-mediated immunity.

Identifiers

PMID41000640
PMCPMC12458350

What Socratic holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

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 Socratic graph.