Evidence map›Paper›PMID 12885870›Full record

ArticleThe Journal of experimental medicine2003

Vav1 phosphorylation is induced by beta2 integrin engagement on natural killer cells upstream of actin cytoskeleton and lipid raft reorganization.

Beatrice Riteau, Domingo F Barber, Eric O Long

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

52 citing papers in PubMed, 120 citations in OpenAlex.

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  10. β2 Integrins-Multi-Functional Leukocyte Receptors in Health and Disease.International journal of molecular sciences · 2020
    Review
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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

3 authors at 1 institution in 1 country.

Beatrice RiteauLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Domingo F Barber
Eric O Long
National Institutes of Health · US

Funding

Regulation of innate lymphocyte functionZIAAI000525 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LONG, ERIC O · 2009 to 2024
$12.0M
MOLECULAR ANALYSIS OF HUMAN NATURAL KILLER CELLSZ01AI000525 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI LONG, ERIC O · 1988 to 2008
$4.7M
Regulation Of Natural Killer Cell ActivityZ01AI000842 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI LONG, ERIC O · 1999 to 2008
$1.9M
6 · The paper itself

Abstract

The guanine nucleotide exchange factor Vav1 regulates actin polymerization and contributes to cytotoxicity by natural killer (NK) cells. An open question is how Vav1 becomes activated and what receptor can signal upstream of actin cytoskeleton rearrangement upon NK cell contact with target cells. Using transfected insect cells that express ligands of human NK cell receptors, we show that engagement of the beta2 integrin LFA-1 on NK cells by intercellular adhesion molecule (ICAM)-1 led to a tyrosine phosphorylation of Vav1 that was not sensitive to cholesterol depletion and to inhibition of actin polymerization. Vav1 phosphorylation was blocked by an inhibitor of Src-family kinases, and correlated with activation of its downstream effector PAK. Binding of activation receptor 2B4 to its ligand CD48 was not sufficient for Vav1 phosphorylation. However, coengagement of 2B4 with LFA-1 resulted in an enhancement of Vav1 phosphorylation that was sensitive to cholesterol depletion and to inhibition of actin polymerization. Vav1 was recruited to a detergent-resistant membrane (DRM) fraction only when 2B4 and LFA-1 were coengaged, but not after LFA-1 engagement. Therefore, binding of LFA-1 to ICAM-1 on target cells may initiate an early signaling cascade in NK cells through activation of Vav1, leading to cytoskeleton reorganization and amplification of signals from other activation receptors.

Indexed as

Cell Cycle ProteinsActinsAnimalsCD18 AntigensCell LineCytoskeletonHumansIntercellular Adhesion Molecule-1Killer Cells, NaturalLymphocyte Function-Associated Antigen-1Membrane MicrodomainsPhosphorylationProtein BindingProto-Oncogene ProteinsProto-Oncogene Proteins c-vavReceptors, ImmunologicActinsCD18 AntigensCell Cycle ProteinsIntercellular Adhesion Molecule-1Lymphocyte Function-Associated Antigen-1Proto-Oncogene ProteinsProto-Oncogene Proteins c-vavReceptors, ImmunologicTyrosineVAV1 protein, human

Identifiers

PMID12885870
PMCPMC2194094
OpenAlexW2054275629

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.