Evidence map›Paper›PMID 10637278›Full record

ArticleThe Journal of experimental medicine2000

A balance between positive and negative signals in cytotoxic lymphocytes regulates the polarization of lipid rafts during the development of cell-mediated killing.

Z Lou, D Jevremovic, D D Billadeau, P J Leibson

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

37 citing papers in PubMed, 130 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

4 authors at 1 institution in 1 country.

Z LouDepartment of Pharmacology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, Minnesota 55905, USA.
D Jevremovic
D D Billadeau
P J Leibson
Mayo Clinic · US

Funding

MECHANISMS OF NATURAL KILLER CELL ACTIVATIONR01CA047752 · NCI · MAYO CLINIC ROCHESTER · PI BILLADEAU, DANIEL D · 1990 to 2012
$3.8M
NCI NIH HHS CA47752NCI NIH HHS R01 CA047752
6 · The paper itself

Abstract

Plasma membrane microdomains containing sphingolipids and cholesterol (lipid rafts) are enriched in signaling molecules. The cross-linking of certain types of cell surface receptors initiates the redistribution of these lipid rafts, resulting in the formation of signaling complexes. However, little is known about the regulation of the initial raft redistribution and whether negative regulatory signaling pathways target this phase of cellular activation. We used natural killer (NK) cells as a model to investigate the regulation of raft redistribution, as both positive and negative signals have been implicated in the development of their cellular function. Here we show that after NK cells form conjugates with sensitive tumor cells, rafts become polarized to the site of target recognition. This redistribution of lipid rafts requires the activation of both Src and Syk family protein tyrosine kinases. In contrast, engagement of major histocompatibility complex (MHC)-recognizing killer cell inhibitory receptors (KIRs) on NK cells by resistant, MHC-bearing tumor targets blocks raft redistribution. This inhibition is dependent on the catalytic activity of KIR-associated SHP-1, a Src homology 2 (SH2) domain containing tyrosine phosphatase. These results suggest that the influence of integrated positive and negative signals on raft redistribution critically influences the development of cell-mediated cytotoxicity.

Indexed as

AnimalsCholesterolCytotoxicity, ImmunologicEnzyme PrecursorsHLA-B AntigensHumansIntracellular Signaling Peptides and ProteinsK562 CellsKiller Cells, NaturalMiceProtein-Tyrosine KinasesProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesReceptors, ImmunologicReceptors, KIRCholesterolEnzyme PrecursorsHLA-B AntigensIntracellular Signaling Peptides and ProteinsProtein-Tyrosine KinasesProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesPTPN11 protein, humanPtpn11 protein, mousePTPN6 protein, humanPtpn6 protein, mouseReceptors, ImmunologicReceptors, KIRSH2 Domain-Containing Protein Tyrosine PhosphatasesSphingolipidssrc-Family KinasesSyk KinaseSYK protein, humanSyk protein, mouse

Identifiers

PMID10637278
PMCPMC2195747
OpenAlexW2132264213

What OpenQuestion holds

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LicenceCC BY-NC-SA
Read underepoch 390

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.