Protease-activated receptor 2

Protease-activated receptor 2 (PAR2) is a member of the protease-activated receptor family, which are a subset of G protein-coupled receptors (GPCRs). These receptors are unique in that they are activated by the cleavage of part of their extracellular domain by specific proteases.

Structure

PAR2 is a transmembrane protein that spans the cell membrane seven times, characteristic of GPCRs. The receptor is activated when a protease cleaves its extracellular N-terminus, revealing a new N-terminus that acts as a tethered ligand, binding intramolecularly to the receptor to initiate signal transduction.

Activation and Signaling

PAR2 can be activated by various proteases, including trypsin, tryptase, and certain coagulation factors. Upon activation, PAR2 couples with G proteins, leading to the activation of multiple intracellular signaling pathways, including the phospholipase C pathway, which results in the production of inositol trisphosphate (IP3) and diacylglycerol (DAG), and the activation of protein kinase C (PKC).

Physiological Roles

PAR2 is expressed in various tissues, including the gastrointestinal tract, skin, lungs, and immune system. It plays a role in numerous physiological processes such as inflammation, pain perception, wound healing, and immune response.

Inflammation

PAR2 is involved in the regulation of inflammatory responses. Activation of PAR2 on immune cells can lead to the release of pro-inflammatory cytokines and chemokines, contributing to the inflammatory process.

Pain Perception

PAR2 activation has been linked to the modulation of pain. It can sensitize nociceptors, the sensory neurons responsible for pain detection, thereby enhancing pain perception.

Wound Healing

PAR2 plays a role in the wound healing process by promoting the migration and proliferation of keratinocytes and fibroblasts, which are essential for tissue repair.

Clinical Significance

Dysregulation of PAR2 signaling has been implicated in various pathological conditions, including chronic inflammatory diseases, cancer, and allergic reactions. As a result, PAR2 is considered a potential therapeutic target for the treatment of these conditions.

See Also

• Protease-activated receptor
• G protein-coupled receptor
• Inflammation
• Pain perception
• Wound healing