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A functional siRNA screen identifies genes modulating angiotensin II-mediated EGFR transactivation

Overview of attention for article published in Journal of Cell Science, January 2013
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Title
A functional siRNA screen identifies genes modulating angiotensin II-mediated EGFR transactivation
Published in
Journal of Cell Science, January 2013
DOI 10.1242/jcs.128280
Pubmed ID
Authors

Amee J. George, Brooke W. Purdue, Cathryn M. Gould, Daniel W. Thomas, Yanny Handoko, Hongwei Qian, Gregory A. Quaife-Ryan, Kylie A. Morgan, Kaylene J. Simpson, Walter G. Thomas, Ross D. Hannan

Abstract

The angiotensin type 1 receptor (AT1R) transactivates the epidermal growth factor receptor (EGFR) to mediate cellular growth, however, the molecular mechanisms involved have not yet been resolved. To address this, we performed a functional siRNA screen of the human kinome in human mammary epithelial cells that demonstrate a robust AT1R-EGFR transactivation. We identified a suite of genes encoding proteins that both positively and negatively regulate AT1R-EGFR transactivation. Many candidates are components of EGFR signalling networks, whereas others, including TRIO, BMX and CHKA, have not been previously linked to EGFR transactivation. Individual knockdown of TRIO, BMX or CHKA attenuated tyrosine phosphorylation of the EGFR by angiotensin II stimulation, but this did not occur following direct stimulation of the EGFR with EGF, indicating that these proteins function between the activated AT1R and the EGFR. Further investigation of TRIO and CHKA revealed that their activity is likely to be required for AT1R-EGFR transactivation. CHKA also mediated EGFR transactivation in response to another G protein-coupled receptor (GPCR) ligand, thrombin, indicating a pervasive role for CHKA in GPCR-EGFR crosstalk. Our study reveals the power of unbiased, functional genomic screens to identify new signalling mediators important for tissue remodelling in cardiovascular disease and cancer.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 82 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 3 4%
Unknown 79 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 30 37%
Other 28 34%
Student > Ph. D. Student 6 7%
Student > Bachelor 5 6%
Professor 2 2%
Other 6 7%
Unknown 5 6%
Readers by discipline Count As %
Agricultural and Biological Sciences 54 66%
Biochemistry, Genetics and Molecular Biology 8 10%
Medicine and Dentistry 5 6%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Immunology and Microbiology 2 2%
Other 4 5%
Unknown 6 7%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 27 November 2013.
All research outputs
#20,655,488
of 25,373,627 outputs
Outputs from Journal of Cell Science
#8,165
of 9,019 outputs
Outputs of similar age
#228,815
of 288,986 outputs
Outputs of similar age from Journal of Cell Science
#178
of 244 outputs
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