Evidence map›Paper›PMID 26186728›Full record

ArticlePloS one2015

Discs Large Homolog 1 Splice Variants Regulate p38-Dependent and -Independent Effector Functions in CD8+ T Cells.

Oscar Silva, Jillian Crocetti, Lisa A Humphries, Janis K Burkhardt, M Carrie Miceli

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

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

7 citing papers in PubMed, 16 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Oscar SilvaDepartment of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
Jillian CrocettiMolecular Biology Interdepartmental Program, University of California Los Angeles, Los Angeles, California, United States of America.
Lisa A HumphriesDepartment of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
Janis K BurkhardtDepartment of Laboratory Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
M Carrie MiceliDepartment of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
University of California, Los Angeles · USUniversity of Pennsylvania · US

Funding

The Function of Tribbles in the Pathogenesis of AMLP01CA093615 · NCI · UNIVERSITY OF PENNSYLVANIA · PI KORETZKY, GARY A. · 2002 to 2011
$16.2M
MULTIDISCIPLINARY TRAINING IN MICROBIAL PATHOGENESIST32AI007323 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peter John Bradley · 1988 to 2026
$8.6M
Coreceptor Modification of TCR Tyrosine Kinase SignalsR01AI067253 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MICELI, M CARRIE · 2005 to 2009
$1.7M
NCI NIH HHS P01 CA093615NIAID NIH HHS R01 AI067253NIAID NIH HHS R01-AI067253NIAID NIH HHS T32 AI007323NIAID NIH HHS T32-AI07323
6 · The paper itself

Abstract

Functionally diverse CD8+ T cells develop in response to antigenic stimulation with differing capacities to couple TCR engagement to downstream signals and functions. However, mechanisms of diversifying TCR signaling are largely uncharacterized. Here we identified two alternative splice variants of scaffold protein Dlg1, Dlg1AB and Dlg1B, that diversify signaling to regulate p38-dependent and -independent effector functions in CD8+ T cells. Dlg1AB, but not Dlg1B associated with Lck, coupling TCR stimulation to p38 activation and proinflammatory cytokine production. Conversely, both Dlg1AB and Dlg1B mediated p38-independent degranulation. Degranulation depended on a Dlg1 fragment containing an intact Dlg1SH3-domain and required the SH3-ligand WASp. Further, Dlg1 controlled WASp activation by promoting TCR-triggered conformational opening of WASp. Collectively, our data support a model where Dlg1 regulates p38-dependent proinflammatory cytokine production and p38-independent cytotoxic granule release through the utilization of alternative splice variants, providing a mechanism whereby TCR engagement couples downstream signals to unique effector functions in CD8+ T cells.

Indexed as

ActinsAlternative SplicingAnimalsCD8-Positive T-LymphocytesCell DegranulationCytokinesDiscs Large Homolog 1 ProteinEnzyme ActivationGene Knockdown TechniquesGranzymesInflammation MediatorsInterferon-gammaInterleukin-2Lymphocyte Specific Protein Tyrosine Kinase p56(lck)MiceNerve Tissue ProteinsActinsCytokinesDiscs Large Homolog 1 ProteinDlg1 protein, mouseGranzymesInflammation MediatorsInterferon-gammaInterleukin-2Lymphocyte Specific Protein Tyrosine Kinase p56(lck)Nerve Tissue ProteinsNFATC Transcription Factorsp38 Mitogen-Activated Protein KinasesReceptors, Antigen, T-CellSAP90-PSD95 Associated ProteinsTumor Necrosis Factor-alphaWiskott-Aldrich Syndrome Protein

Identifiers

PMID26186728
PMCPMC4505885
OpenAlexW888094841

What Socratic holds

Textmetadata
LicenceCC BY
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.