Evidence map›Paper›PMID 26018935›Full record

ArticleGene therapy2015

Enhanced T-cell activation and differentiation in lymphocytes from transgenic mice expressing ubiquitination-resistant 2KR LAT molecules.

A B Rodriguez-Peña, J Gomez-Rodriguez, R L Kortum, D C Palmer, Z Yu, G C Guittard, E A Wohlfert, P B Silver, J A Misplon, C L Sommers and 7 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.4field-weighted citation impact, top 37% of its field
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

10 citing papers in PubMed, 10 citations in OpenAlex.

  1. Advances inMolecular therapy. Nucleic acids · 2026
    Review
  2. Review
  3. Review
  4. Review
  5. Microclusters as T Cell Signaling Hubs: Structure, Kinetics, and Regulation.Frontiers in cell and developmental biology · 2020
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 9 institutions in 2 countries.

A B Rodriguez-PeñaLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
J Gomez-RodriguezCell Signaling and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
R L KortumLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
D C PalmerTumor Immunology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Z YuTumor Immunology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
G C GuittardLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
E A WohlfertImmunity at Barrier Sites Initiative, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
P B SilverImmunoregulation Section, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
J A MisplonCenter for Biologics Evaluation & Research, Food and Drug Administration, Silver Spring, MD, USA.
C L SommersLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
L FeigenbaumLaboratory Animal Sciences Program, Leidos Biomedical Research Inc, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
S L EpsteinCenter for Biologics Evaluation & Research, Food and Drug Administration, Silver Spring, MD, USA.
R R CaspiImmunoregulation Section, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Y BelkaidImmunity at Barrier Sites Initiative, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
N P RestifoTumor Immunology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
L E SamelsonLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
L BalagopalanLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
National Institutes of Health · USCenter for Biologics Evaluation and Research · USCenter for Cancer Research · USNational Cancer Institute · USNational Eye Institute · USCentro de Investigación del Cáncer · ESFrederick National Laboratory for Cancer Research · USNational Human Genome Research Institute · USUniversity at Buffalo, State University of New York · US

Funding

Genetic, Cellular and Molecular Mechanisms in Autoimmunity to RetinaZIAEY000184 · NEI · NATIONAL EYE INSTITUTE · PI CASPI, RACHEL R. · 2009 to 2025
$51.7M
Biochemical Basis of T Cell ActivationZIABC010304 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SAMELSON, LAWRENCE · 2009 to 2025
$36.3M
Building on the success of the adoptive immunotherapy of cancerZIABC010763 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROSENBERG, STEVEN · 2009 to 2020
$25.0M
Genetic and Biochemical Approaches to Tyrosine Kinase FunctionZIAHG000123 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SCHWARTZBERG, PAMELA · 2009 to 2018
$20.8M
Role of Tissue-Specific Factors in the Control of ImmunityZIAAI001132 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BELKAID, YASMINE · 2011 to 2025
$6.4M
Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

Linker for activation of T cells (LAT) is critical for the propagation of T-cell signals upon T-cell receptor (TCR) activation. Previous studies demonstrated that substitution of LAT lysines with arginines (2KR LAT) resulted in decreased LAT ubiquitination and elevated T-cell signaling, indicating that LAT ubiquitination is a molecular checkpoint for attenuation of T-cell signaling. To investigate the role of LAT ubiquitination in vivo, we have generated transgenic mice expressing WT and ubiquitin-defective 2KR LAT. On TCR stimulation of T cells from these mice, proximal signaling and cytokine production was elevated in 2KR versus wild-type (WT) LAT mice. Enhanced cytolytic activity as well as T-helper responses were observed on LAT expression, which were further elevated by 2KR LAT expression. Despite greater T-effector function, WT or 2KR LAT expression did not have any effect on clearance of certain pathogens or tumors. Our data support the model that lack of tumor clearance is due to increased differentiation and acquisition of effector phenotype that is associated with suboptimal immunity in an immunotherapy model. Thus, our data further reinforce the role of LAT ubiquitination in TCR signaling and uncovers a novel role for LAT in driving T-cell differentiation.

Indexed as

Lymphocyte ActivationAdaptor Proteins, Signal TransducingAmino Acid SubstitutionAnimalsCell DifferentiationLymphocytesMembrane ProteinsMiceMice, TransgenicPhosphoproteinsReceptors, Antigen, T-CellUbiquitinationAdaptor Proteins, Signal TransducingLat protein, mouseMembrane ProteinsPhosphoproteinsReceptors, Antigen, T-Cell

Identifiers

PMID26018935
PMCPMC6291846
OpenAlexW2077326081

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.