Evidence map›Paper›PMID 23284735›Full record

ArticlePloS one2012

A mechanistic model of early FcεRI signaling: lipid rafts and the question of protection from dephosphorylation.

Dipak Barua, Byron Goldstein

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.5field-weighted citation impact, top 36% 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

17 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
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  9. Review
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  11. Article
  12. The Continuing Mystery of Lipid Rafts.Journal of molecular biology · 2016
    Review
  13. Article
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  15. Review
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Dipak BaruaTheoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Byron Goldstein
Los Alamos National Laboratory · US

Funding

Receptor Aggregation and Its EffectsR37GM035556 · NIGMS · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI GOLDSTEIN, BYRON B · 2003 to 2012
$6.4M
NIGMS NIH HHS R37 GM035556NIGMS NIH HHS R37-GM035556
6 · The paper itself

Abstract

We present a model of the early events in mast cell signaling mediated by FcεRI where the plasma membrane is composed of many small ordered lipid domains (rafts), surrounded by a non-order region of lipids consisting of the remaining plasma membrane. The model treats the rafts as transient structures that constantly form and breakup, but that maintain a fixed average number per cell. The rafts have a high propensity for harboring Lyn kinase, aggregated, but not unaggregated receptors, and the linker for the activation of T cells (LAT). Phosphatase activity in the rafts is substantially reduced compared to the nonraft region. We use the model to analyze published experiments on the rat basophilic leukemia (RBL)-2H3 cell line that seem to contradict the notion that rafts offer protection. In these experiments IgE was cross-linked with a multivalent antigen and then excess monovalent hapten was added to break-up cross-links. The dephosphorylation of the unaggregated receptor (nonraft associated) and of LAT (raft associated) were then monitored in time and found to decay at similar rates, leading to the conclusion that rafts offer no protection from dephosphorylation. In the model, because the rafts are transient, a protein that is protected while in a raft will be subject to dephosphorylation when the raft breaks up and the protein finds itself in the nonraft region of the membrane. We show that the model is consistent with the receptor and LAT dephosphorylation experiments while still allowing rafts to enhance signaling by providing substantial protection from phosphatases.

Indexed as

Models, BiologicalAnimalsCalciumCell MembraneComputer SimulationHaptensImmunoglobulin EIntracellular Signaling Peptides and ProteinsLeukemia, Basophilic, AcuteLipoylationMast CellsMembrane MicrodomainsMutationPhosphorylationProtein-Tyrosine KinasesRatsCalciumFCER1A protein, ratHaptensImmunoglobulin EIntracellular Signaling Peptides and Proteinslyn protein-tyrosine kinaseProtein-Tyrosine KinasesReceptors, IgEsrc-Family KinasesSyk KinaseSyk protein, ratTyrosine

Identifiers

PMID23284735
PMCPMC3524258
OpenAlexW2013032123

What OpenQuestion holds

Textmetadata
LicenceCC0
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.