Evidence map›Paper›PMID 24904059›Full record

ArticleThe Journal of biological chemistry2014

Regulation of Fc∈RI signaling in mast cells by G protein-coupled receptor kinase 2 and its RH domain.

Hariharan Subramanian, Kshitij Gupta, Narayanan Parameswaran, Hydar Ali

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

14 citing papers in PubMed, 18 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 2 institutions in 1 country.

Hariharan Subramanian
Kshitij Gupta
Narayanan Parameswaran
Hydar Ali
University of Pennsylvania · USMichigan State University · US

Funding

GPCR Kinase-2 in TNFalpha Signaling in MacrophagesR01HL095637 · NHLBI · MICHIGAN STATE UNIVERSITY · PI PARAMESWARAN, NARAYANAN · 2009 to 2013
$1.8M
G Protein Coupled Receptor Signaling in Mast CellsR01HL085774 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ALI, HYDAR · 2008 to 2011
$1.6M
A novel role for the adapter molecule NHERF1 in regulating asthma and allergic reR00HL121073 · NHLBI · MICHIGAN STATE UNIVERSITY · PI SUBRAMANIAN, HARIHARAN · 2016 to 2018
$734k
G-Protein Coupled Receptor Kinase-2 on IgE Signaling in Mast CellsR21AI094896 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ALI, HYDAR · 2011 to 2012
$440k
GPCR Kinase-5 in Inflammatory Bowel DiseaseR21AI099404 · NIAID · MICHIGAN STATE UNIVERSITY · PI PARAMESWARAN, NARAYANAN · 2013 to 2014
$397k
A novel role for the adapter molecule NHERF1 in regulating asthma and allergic reK99HL121073 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SUBRAMANIAN, HARIHARAN · 2014 to 2015
$216k
NHLBI NIH HHS HL085774NHLBI NIH HHS K99 HL121073NHLBI NIH HHS K99-HL121073NHLBI NIH HHS R00 HL121073NHLBI NIH HHS R01 HL085774NHLBI NIH HHS R01 HL095637NIAID NIH HHS AI094896NIAID NIH HHS R21 AI094896NIAID NIH HHS R21 AI099404
6 · The paper itself

Abstract

Agonist-induced phosphorylation of G protein-coupled receptors (GPCRs) by GPCRkinases (GRKs) promotes their desensitization and internalization. Here, we sought to determine the role of GRK2 on Fc∈RI signaling and mediator release in mast cells. The strategies utilized included lentiviral shRNA-mediated GRK2 knockdown, GRK2 gene deletion (GRK2(flox/flox)/cre recombinase) and overexpression of GRK2 and its regulator of G protein signaling homology (RH) domain (GRK2-RH). We found that silencing GRK2 expression caused ~50% decrease in antigen-induced Ca(2+) mobilization and degranulation but resulted in ablation of cytokine (IL-6 and IL-13) generation. The effect of GRK2 on cytokine generation does not require its catalytic activity but is mediated via the phosphorylation of p38 and Akt. Overexpression of GRK2 or its RH domain (GRK2-RH) enhanced antigen-induced mast cell degranulation and cytokine generation without affecting the expression levels of any of the Fc∈RI subunits (α, β, and γ). GRK2 or GRK2-RH had no effect on antigen-induced phosphorylation of Fc∈RIγ or Src but enhanced tyrosine phosphorylation of Syk. These data demonstrate that GRK2 modulates Fc∈RI signaling in mast cells via at least two mechanisms.One involves GRK2-RH and modulates tyrosine phosphorylation of Syk, and the other is mediated via the phosphorylation of p38 and Akt.

Indexed as

AnimalsCell DegranulationCell LineGene DeletionGene SilencingG-Protein-Coupled Receptor Kinase 2HumansInterleukin-13Interleukin-6Intracellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemMast CellsMice, Transgenicp38 Mitogen-Activated Protein KinasesPhosphorylationProtein Structure, TertiaryG-Protein-Coupled Receptor Kinase 2GRK2 protein, humanGRK2 protein, mouseIL6 protein, humanInterleukin-13Interleukin-6Intracellular Signaling Peptides and Proteinsp38 Mitogen-Activated Protein KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-aktReceptors, IgESyk KinaseSYK protein, humanSyk protein, mouse

Identifiers

PMID24904059
PMCPMC4110298
OpenAlexW2075958276

What OpenQuestion holds

Textmetadata
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.