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

George, Amee J., Purdue, Brooke W., Gould, Cathryn M., Thomas, Daniel W., Handoko, Yanny, Qian, Hongwei, Quaife-Ryan, Gregory A., Morgan, Kylie A., Simpson, Kaylene J., Thomas, Walter G. and Hannan, Ross D. (2013) A functional siRNA screen identifies genes modulating angiotensin II-mediated EGFR transactivation. Journal of Cell Science, 126 23: 5377-5390. doi:10.1242/jcs.128280

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ320066_OA.pdf Full text (open access) application/pdf 3.21MB 0

Author George, Amee J.
Purdue, Brooke W.
Gould, Cathryn M.
Thomas, Daniel W.
Handoko, Yanny
Qian, Hongwei
Quaife-Ryan, Gregory A.
Morgan, Kylie A.
Simpson, Kaylene J.
Thomas, Walter G.
Hannan, Ross D.
Title A functional siRNA screen identifies genes modulating angiotensin II-mediated EGFR transactivation
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 0021-9533
Publication date 2013-12-01
Year available 2013
Sub-type Article (original research)
DOI 10.1242/jcs.128280
Open Access Status File (Publisher version)
Volume 126
Issue 23
Start page 5377
End page 5390
Total pages 14
Place of publication Cambridge, United Kingdom
Publisher Company of Biologists
Language eng
Subject 1307 Cell Biology
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.
Keyword Angiotensin
G protein-coupled receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 472640
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 19 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 19 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 29 Dec 2013, 10:08:03 EST by System User on behalf of School of Biomedical Sciences