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H2O2 Production Downstream of FLT3 Is Mediated by p22phox in the Endoplasmic Reticulum and Is Required for STAT5 Signalling

Overview of attention for article published in PLOS ONE, July 2012
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (82nd percentile)
  • Good Attention Score compared to outputs of the same age and source (77th percentile)

Mentioned by

blogs
1 blog
twitter
1 tweeter

Citations

dimensions_citation
47 Dimensions

Readers on

mendeley
71 Mendeley
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Title
H2O2 Production Downstream of FLT3 Is Mediated by p22phox in the Endoplasmic Reticulum and Is Required for STAT5 Signalling
Published in
PLOS ONE, July 2012
DOI 10.1371/journal.pone.0034050
Pubmed ID
Authors

John F. Woolley, Ruth Naughton, Joanna Stanicka, David R. Gough, Lavinia Bhatt, Bryan C. Dickinson, Christopher J. Chang, Thomas G. Cotter

Abstract

The internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor has been associated with increased reactive oxygen species (ROS) generation in acute myeloid leukemia (AML). How this elevated level of ROS contributes to the leukemic phenotype, however, remains poorly understood. In this work we show that ROS in the FLT3-ITD expressing AML cell line MV4-11 is reduced by treatment with PKC412, an inhibitor of FLT3, DPI, a flavoprotein inhibitor, and VAS2870, a Nox specific inhibitor, suggesting that ROS production is both FLT3 and NADPH oxidase dependent. The majority of these ROS co-localize to the endoplasmic reticulum (ER), as determined with the H(2)O(2)-specific aryl-boronate dye Peroxyorange 1, which also corresponds to co-localization of p22phox. Moreover, knocking down p22phox dramatically reduces H(2)O(2) after 24 hours in the ER, without affecting mitochondrial ROS. Significantly, the FLT3 inhibitor PKC412 reduces H(2)O(2) in FLT3-ITD expressing cell lines (MV4-11, MOLM-13) through reduction of p22phox over 24 hours. Reduced p22phox is achieved by proteasomal degradation and is prevented upon GSK3-β inhibition. Knockdown of p22phox resulted in reduced STAT5 signalling and reduced Pim-1 levels in the cells after 24 hours. Thus, we have shown that FLT3 driven H(2)O(2) production in AML cells is mediated by p22phox and is critical for STAT5 signalling.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 71 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
Switzerland 1 1%
Unknown 69 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 24 34%
Researcher 13 18%
Student > Master 7 10%
Professor 6 8%
Student > Bachelor 5 7%
Other 9 13%
Unknown 7 10%
Readers by discipline Count As %
Agricultural and Biological Sciences 27 38%
Medicine and Dentistry 11 15%
Biochemistry, Genetics and Molecular Biology 10 14%
Chemistry 9 13%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 3 4%
Unknown 9 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 April 2017.
All research outputs
#3,617,693
of 20,585,116 outputs
Outputs from PLOS ONE
#45,602
of 177,676 outputs
Outputs of similar age
#24,233
of 141,083 outputs
Outputs of similar age from PLOS ONE
#747
of 3,386 outputs
Altmetric has tracked 20,585,116 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 177,676 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.4. This one has gotten more attention than average, scoring higher than 74% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 141,083 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 82% of its contemporaries.
We're also able to compare this research output to 3,386 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.