RNA sequencing to determine the contribution of kinase receptor transactivation to G protein coupled receptor signalling in vascular smooth muscle cells

Kamato, D, Bhaskarla, V, Mantri, N, Oh, T, Ling, D, Janke, R, Zheng, W, Little AM, P and Osman, N 2017, 'RNA sequencing to determine the contribution of kinase receptor transactivation to G protein coupled receptor signalling in vascular smooth muscle cells', PLoS One, vol. 12, no. 7, e0180842, pp. 1-28.


Document type: Journal Article
Collection: Journal Articles

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Title RNA sequencing to determine the contribution of kinase receptor transactivation to G protein coupled receptor signalling in vascular smooth muscle cells
Author(s) Kamato, D
Bhaskarla, V
Mantri, N
Oh, T
Ling, D
Janke, R
Zheng, W
Little AM, P
Osman, N
Year 2017
Journal name PLoS One
Volume number 12
Issue number 7
Article Number e0180842
Start page 1
End page 28
Total pages 28
Publisher Public Library of Science
Abstract G protein coupled receptor (GPCR) signalling covers three major mechanisms. GPCR agonist engagement allows for the G proteins to bind to the receptor leading to a classical downstream signalling cascade. The second mechanism is via the utilization of the β-arrestin signalling molecule and thirdly via transactivation dependent signalling. GPCRs can transactivate protein tyrosine kinase receptors (PTKR) to activate respective downstream signalling intermediates. In the past decade GPCR transactivation dependent signalling was expanded to show transactivation of serine/threonine kinase receptors (S/TKR). Kinase receptor transactivation enormously broadens the GPCR signalling paradigm. This work utilizes next generation RNA-sequencing to study the contribution of transactivation dependent signalling to total protease activated receptor (PAR)-1 signalling. Transactivation, assessed as gene expression, accounted for 50 percent of the total genes regulated by thrombin acting through PAR-1 in human coronary artery smooth muscle cells. GPCR transactivation of PTKRs is approximately equally important as the transactivation of the S/TKR with 209 and 177 genes regulated respectively, via either signalling pathway. This work shows that genome wide studies can provide powerful insights into GPCR mediated signalling pathways.
Subject Cardiology (incl. Cardiovascular Diseases)
Gene Expression (incl. Microarray and other genome-wide approaches)
DOI - identifier 10.1371/journal.pone.0180842
Copyright notice © 2017 Kamato et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ISSN 1932-6203
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