Insights into cellular signalling by G protein coupled receptor transactivation of cell surface protein kinase receptors.
G protein coupled receptor (GPCR) signalling is mediated by transactivation independent and transactivation dependent pathways. GPCRs transactivate protein tyrosine kinase receptors (PTKRs) and protein serine/threonine kinase receptors (PS/TKR). Since the initial observations of transactivation dependent signalling, there has been an effort to understand the mechanisms behind this phenomena. GPCR signalling has evolved to include biased signalling. Biased signalling, whereby selected ligands can activate the same GPCR that can generate multiple signals, but drive only a unique response. To date, there has been no focus on the ability of biased agonists to activate the PTKR and PS/TKR transactivation pathways differentially. As such, this represents a novel direction for future research. This review will discuss the main mechanisms of GPCR mediated receptor transactivation and the pathways involved in intracellular responses.
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD 4102, Australia.
Rebecca
R
Chaplin
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD 4102, Australia.
Lyna
L
Thach
Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
Morley D
MD
Hollenberg
Xinhua College, Sun Yat-sen University, Tianhe District, Guangzhou, 510520, China.
Yingnan
Y
Cao
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD 4102, Australia.|Xinhua College, Sun Yat-sen University, Tianhe District, Guangzhou, 510520, China.
Peter J
PJ
Little
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD 4102, Australia. d.kamato@uq.edu.au.
Danielle
http://orcid.org/0000-0002-1089-2829
D
Kamato
Biased signalling; G-protein coupled receptors; Heterotrimeric G proteins; Serine/threonine kinase receptors; Transactivation signalling