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A Functional Kinase Short Interfering Ribonucleic Acid Screen Using Protease-Activated Receptor 2-Dependent Opening of Transient Receptor Potential Vanilloid-4

Overview of attention for article published in Assay and Drug Development Technologies, November 2017
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Title
A Functional Kinase Short Interfering Ribonucleic Acid Screen Using Protease-Activated Receptor 2-Dependent Opening of Transient Receptor Potential Vanilloid-4
Published in
Assay and Drug Development Technologies, November 2017
DOI 10.1089/adt.2017.799
Pubmed ID
Authors

William G. Darby, Megan S. Grace, Kaylene J. Simpson, Owen L. Woodman, Peter McIntyre

Abstract

Protease-activated receptor 2 (PAR2) is a proinflammatory G-protein coupled receptor (GPCR) that is activated by inflammatory proteases, and its activation initiates signaling pathways that modulate the nonselective cation channel transient receptor potential vanilloid-4 (TRPV4). PAR2-dependent opening of TRPV4 has been attributed to kinase activation, but the identity of the responsible enzymes is unknown. Deciphering the signaling pathways involved in the PAR2-dependent opening of TRPV4 may yield new targets for pain treatment. This study has identified specific kinases that are involved in opening TRPV4, using a selective screen of short interfering ribonucleic acid (siRNA) SMARTpools, which individually targeted all human kinases, in human embryonic kidney 293 (HEK293) cells that stably express inducible TRPV4. This screen is unique because it uses a real-time assay measuring intracellular calcium with Fura-2AM dye. From the primary screen, subsequent confirmation screen, and on-target messenger ribonucleic acid expression analysis, we identified two kinases as crucial to the PAR2-dependent opening of TRPV4 in HEK293 cells, mitogen-activated protein kinase 13 and with no lysine kinase 4. In conclusion, this study describes a powerful new application of siRNA knockdown to identity signaling molecules that are responsible for the PAR2-dependent opening of TRPV4, which will help elucidate this signaling process.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 10 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 30%
Researcher 2 20%
Professor 1 10%
Student > Master 1 10%
Student > Doctoral Student 1 10%
Other 0 0%
Unknown 2 20%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 3 30%
Biochemistry, Genetics and Molecular Biology 2 20%
Medicine and Dentistry 2 20%
Agricultural and Biological Sciences 1 10%
Unknown 2 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 18 November 2017.
All research outputs
#16,051,091
of 25,382,440 outputs
Outputs from Assay and Drug Development Technologies
#317
of 462 outputs
Outputs of similar age
#245,837
of 438,959 outputs
Outputs of similar age from Assay and Drug Development Technologies
#4
of 9 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 462 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
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 438,959 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 9 others from the same source and published within six weeks on either side of this one. This one has scored higher than 5 of them.