Next Article in Journal
Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease
Next Article in Special Issue
A Rapid and Efficient Immunoenzymatic Assay to Detect Receptor Protein Interactions: G Protein-Coupled Receptors
Previous Article in Journal
Synthesis of Cellulose-2,3-bis(3,5-dimethylphenylcarbamate) in an Ionic Liquid and Its Chiral Separation Efficiency as Stationary Phase
Previous Article in Special Issue
Single and Binge Methamphetamine Administrations Have Different Effects on the Levels of Dopamine D2 Autoreceptor and Dopamine Transporter in Rat Striatum
Open AccessReview

Differential Signaling by Protease-Activated Receptors: Implications for Therapeutic Targeting

Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne 3004, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2014, 15(4), 6169-6183; https://doi.org/10.3390/ijms15046169
Received: 20 December 2013 / Revised: 14 March 2014 / Accepted: 3 April 2014 / Published: 11 April 2014
(This article belongs to the Collection G Protein-Coupled Receptor Signaling and Regulation)
Protease-activated receptors (PARs) are a family of four G protein-coupled receptors that exhibit increasingly appreciated differences in signaling and regulation both within and between the receptor class. By nature of their proteolytic self-activation mechanism, PARs have unique processes of receptor activation, “ligand” binding, and desensitization/resensitization. These distinctive aspects have presented both challenges and opportunities in the targeting of PARs for therapeutic benefit—the most notable example of which is inhibition of PAR1 on platelets for the prevention of arterial thrombosis. However, more recent studies have uncovered further distinguishing features of PAR-mediated signaling, revealing mechanisms by which identical proteases elicit distinct effects in the same cell, as well as how distinct proteases produce different cellular consequences via the same receptor. Here we review this differential signaling by PARs, highlight how important distinctions between PAR1 and PAR4 are impacting on the progress of a new class of anti-thrombotic drugs, and discuss how these more recent insights into PAR signaling may present further opportunities for manipulating PAR activation and signaling in the development of novel therapies. View Full-Text
Keywords: protease-activated receptors; G protein-coupled receptors; cell signaling; platelets; thrombosis protease-activated receptors; G protein-coupled receptors; cell signaling; platelets; thrombosis
MDPI and ACS Style

Sidhu, T.S.; French, S.L.; Hamilton, J.R. Differential Signaling by Protease-Activated Receptors: Implications for Therapeutic Targeting. Int. J. Mol. Sci. 2014, 15, 6169-6183.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Back to TopTop