Evidence map›Paper›PMID 28855374›Full record

ArticleMolecular biology of the cell2017

Differential mast cell outcomes are sensitive to FcεRI-Syk binding kinetics.

Samantha L Schwartz, Cédric Cleyrat, Mark J Olah, Peter K Relich, Genevieve K Phillips, William S Hlavacek, Keith A Lidke, Bridget S Wilson, Diane S Lidke

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

29 citing papers in PubMed, 42 citations in OpenAlex.

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  17. Dephosphorylation accelerates the dissociation of ZAP70 from the T cell receptor.Proceedings of the National Academy of Sciences of the United States of America · 2022
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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

9 authors at 2 institutions in 1 country.

Samantha L SchwartzDepartment of Pathology, University of New Mexico, Albuquerque, NM 87131.
Cédric CleyratDepartment of Pathology, University of New Mexico, Albuquerque, NM 87131.
Mark J OlahDepartment of Physics, University of New Mexico, Albuquerque, NM 87131.
Peter K RelichDepartment of Physics, University of New Mexico, Albuquerque, NM 87131.
Genevieve K PhillipsDepartment of Pathology, University of New Mexico, Albuquerque, NM 87131.
William S HlavacekTheoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545.
Keith A LidkeComprehensive Cancer Center, University of New Mexico, Albuquerque, NM 87131.
Bridget S WilsonDepartment of Pathology, University of New Mexico, Albuquerque, NM 87131.
Diane S LidkeDepartment of Pathology, University of New Mexico, Albuquerque, NM 87131 dlidke@salud.unm.edu.
University of New Mexico · USLos Alamos National Laboratory · US

Funding

WOMEN'S CANCERS RESEARCH PROGRAMP30CA118100 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Yolanda Sanchez · 2005 to 2026
$57.1M
UNM TRAININGP50GM085273 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI LIDKE, KEITH A · 2009 to 2018
$26.1M
Single Molecule Imaging to Quantify FcεRI Signaling DynamicsR01GM100114 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI LIDKE, DIANE · 2012 to 2016
$1.4M
NCI NIH HHS P30 CA118100NIGMS NIH HHS P50 GM085273NIGMS NIH HHS R01 GM100114
6 · The paper itself

Abstract

Cross-linking of immunoglobulin E-bound FcεRI triggers multiple cellular responses, including degranulation and cytokine production. Signaling is dependent on recruitment of Syk via docking of its dual SH2 domains to phosphorylated tyrosines within the FcεRI immunoreceptor tyrosine-based activation motifs. Using single-molecule imaging in live cells, we directly visualized and quantified the binding of individual mNeonGreen-tagged Syk molecules as they associated with the plasma membrane after FcεRI activation. We found that Syk colocalizes transiently to FcεRI and that Syk-FcεRI binding dynamics are independent of receptor aggregate size. Substitution of glutamic acid for tyrosine between the Syk SH2 domains (Syk-Y130E) led to an increased Syk-FcεRI off-rate, loss of site-specific Syk autophosphorylation, and impaired downstream signaling. Genome edited cells expressing only Syk-Y130E were deficient in antigen-stimulated calcium release, degranulation, and production of some cytokines (TNF-a, IL-3) but not others (MCP-1, IL-4). We propose that kinetic discrimination along the FcεRI signaling pathway occurs at the level of Syk-FcεRI interactions, with key outcomes dependent upon sufficiently long-lived Syk binding events.

Indexed as

AnimalsCell DegranulationCell Line, TumorImmunoglobulin EIntracellular Signaling Peptides and ProteinsKineticsMast CellsPhosphorylationProtein-Tyrosine KinasesRatsReceptors, IgESignal TransductionSingle Molecule Imagingsrc Homology DomainsSyk KinaseTyrosineFCER1A protein, ratImmunoglobulin EIntracellular Signaling Peptides and ProteinsProtein-Tyrosine KinasesReceptors, IgESyk KinaseSyk protein, ratTyrosine

Identifiers

PMID28855374
PMCPMC5687039
OpenAlexW2951383966

What OpenQuestion holds

Textmetadata
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.