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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

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Insights into cellular signalling by G protein coupled receptor transactivation of cell surface protein kinase

Rebecca Chaplin1, Lyna Thach1, Morley D Hollenberg2

  • 1School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD 4102, Australia.

Journal of Cell Communication and Signaling
|February 8, 2017
PubMed

Insights

G protein-coupled receptors (GPCRs) signal through various pathways, including receptor transactivation. Biased agonists offer a novel research avenue for differentially activating these transactivation pathways.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) mediate cellular responses through distinct signaling pathways.
  • GPCRs can transactivate protein tyrosine kinase receptors (PTKRs) and protein serine/threonine kinase receptors (PS/TKRs).
  • Biased signaling allows specific ligands to elicit unique responses from a single GPCR.

Purpose of the Study:

  • To review the primary mechanisms of GPCR-mediated receptor transactivation.
  • To explore the intracellular pathways involved in GPCR signaling.
  • To highlight the unexplored potential of biased agonists in differentially activating PTKR and PS/TKR transactivation pathways.

Main Methods:

  • Literature review of GPCR signaling mechanisms.
  • Analysis of transactivation-dependent and independent pathways.
  • Discussion of biased signaling in the context of receptor transactivation.

Main Results:

  • GPCRs engage in both transactivation-independent and -dependent signaling cascades.
  • Receptor transactivation involves both PTKRs and PS/TKRs.
  • Biased agonists represent a novel area for investigating differential transactivation pathway activation.

Conclusions:

  • Understanding GPCR transactivation mechanisms is crucial for deciphering complex cellular signaling.
  • Biased signaling offers a new perspective on GPCR-mediated transactivation, with potential therapeutic implications.
  • Future research should focus on the differential activation of PTKR and PS/TKR pathways by biased GPCR agonists.
Keywords:
Biased signallingG-protein coupled receptorsHeterotrimeric G proteinsSerine/threonine kinase receptorsTransactivation signalling

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