Related Experiment Video
Updated: Nov 18, 2025
07:13
Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
Published on: May 24, 2024
737
Protease-activated receptors: An illustrated review
Xu Han1, Marvin T Nieman1, Bryce A Kerlin2,3
1Department of Pharmacology Case Western Reserve University Cleveland OH USA.
Research and Practice in Thrombosis and Haemostasis
|February 4, 2021
Summary
Protease-activated receptors (PARs) are crucial cell signaling molecules activated by proteases. This review covers 30 years of PAR research, highlighting their unique activation, diverse signaling, and clinical relevance.
Area of Science:
- Cellular Biology
- Molecular Signaling
- Biochemistry
Background:
- Proteases regulate cell functions including survival and apoptosis.
- Protease-activated receptors (PARs) are G-protein-coupled receptors activated by proteolysis.
- PAR activation involves a unique tethered ligand mechanism, initiating irreversible signaling.
Purpose of the Study:
- To review key advancements in PAR research over the past three decades.
- To illustrate PAR expression, activation mechanisms, and regulation.
- To explore the clinical translational aspects of PAR biology.
Main Methods:
- Illustrated review of published literature on PARs.
- Analysis of PAR expression profiles across species and human tissues.
- Depiction of PAR signaling pathways, regulation, and pharmacologic interventions.
Main Results:
- PARs, particularly PAR1, are activated by various proteases beyond thrombin.
- PAR activation leads to diverse downstream signaling outcomes dependent on context.
- PAR signaling is regulated by endocytosis and targeted by pharmacologic approaches.
Conclusions:
- PARs represent a critical interface between proteolysis and cellular responses.
- Understanding PAR diversity and regulation is key to therapeutic development.
- Clinical applications of PAR modulation, including pharmacologic and genetic approaches, are emerging.
Related Concept Videos
01:15G Protein-coupled Receptors
15.1K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
15.1K
01:22Amplifying Signals via Enzymatic Cascade
15.3K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
15.3K
01:00Enzyme-linked Receptors
82.8K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
82.8K
01:12GPCR Desensitization
7.2K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
7.2K
01:27Transducer Mechanism: Enzyme-Linked Receptors
3.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
3.5K
01:30Transducer Mechanism: G Protein–Coupled Receptors
3.3K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
3.3K