Evidence map›Paper›PMID 26519537›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2015

Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2.

Kyle L O'Hagan, Jie Zhao, Olga Pryshchep, Chyung-Ru Wang, Hyewon Phee

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Genetic mutation and immune infiltration in embryonal tumor with multilayered rosettes.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024
    Article
  2. Nur77 Mediates Anaphylaxis by Regulating miR-21a.Current issues in molecular biology · 2024
    Article
  3. Genetic Analysis of iNKT Cell Development and Function.Methods in molecular biology (Clifton, N.J.) · 2021
    Review
  4. Review
  5. Article
  6. The role of zinc and its compounds in leukemia.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018
    Review
  7. Review
  8. Article
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.

Kyle L O'HaganDepartment of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.ORCID http://orcid.org/0000-0003-0460-4410
Jie ZhaoDepartment of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Olga PryshchepDepartment of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Chyung-Ru WangDepartment of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Hyewon PheeDepartment of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 hyewonp@amgen.com.ORCID http://orcid.org/0000-0002-1942-0414

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
The Regulation and Function of Murine CD1 MoleculesR01AI043407 · NIAID · UNIVERSITY OF CHICAGO · PI WANG, CHYUNG-RU · 1998 to 2017
$5.2M
The GIT2-PIX-PAK complex in T cell migration, activation and arthritisK01AR059754 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PHEE, HYEWON · 2010 to 2014
$598k
NCI NIH HHS P30 CA060553NIAID NIH HHS R01 AI043407NIAMS NIH HHS 5K01AR059754NIAMS NIH HHS K01 AR059754
6 · The paper itself

Abstract

NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression.

Indexed as

AnimalsAntigens, CDCell DifferentiationEarly Growth Response Protein 2Green Fluorescent ProteinsKruppel-Like Transcription FactorsLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutNatural Killer T-CellsNuclear Receptor Subfamily 4, Group A, Member 1p21-Activated KinasesPromyelocytic Leukemia Zinc Finger ProteinReceptors, Antigen, T-CellReceptors, Cell SurfaceAntigens, CDEarly Growth Response Protein 2Egr2 protein, mouseGreen Fluorescent ProteinsKruppel-Like Transcription FactorsNr4a1 protein, mouseNuclear Receptor Subfamily 4, Group A, Member 1p21-Activated KinasesPak2 protein, mousePromyelocytic Leukemia Zinc Finger ProteinReceptors, Antigen, T-CellReceptors, Cell SurfaceSignaling Lymphocytic Activation Molecule Family Member 1Zbtb16 protein, mouse

Identifiers

PMID26519537
PMCPMC4654230

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Registered trials

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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.