thrombin-activated receptor signaling pathway

Definition

Target type: biologicalprocess

A G protein-coupled receptor signaling pathway initiated by thrombin binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process. [GOC:mah, PMID:1672265]

Thrombin, a serine protease produced by the coagulation cascade, activates protease-activated receptors (PARs), a family of G protein-coupled receptors, by cleaving their N-terminal extracellular domain. This cleavage exposes a new N-terminus, acting as a tethered ligand that binds to the receptor, triggering intracellular signaling cascades. PARs, particularly PAR1 and PAR4, are key mediators of thrombin signaling in platelets, endothelial cells, and other cell types.

Upon activation, PARs initiate a series of events involving G protein signaling, phospholipase C activation, and calcium mobilization. This leads to the activation of downstream signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway, the phosphoinositide 3-kinase (PI3K) pathway, and the Rho GTPase pathway.

The thrombin-activated receptor signaling pathway plays a crucial role in various physiological processes:

* **Platelet aggregation and hemostasis:** Thrombin activates PARs on platelets, triggering their aggregation and the formation of a platelet plug, essential for hemostasis.
* **Inflammation and vascular permeability:** Thrombin activates PARs on endothelial cells, leading to increased vascular permeability and the recruitment of inflammatory cells.
* **Cell proliferation and migration:** Thrombin-activated receptor signaling contributes to cell proliferation and migration in various cell types, including smooth muscle cells, fibroblasts, and endothelial cells.
* **Wound healing:** Thrombin signaling promotes wound healing by stimulating angiogenesis, cell migration, and extracellular matrix deposition.

Dysregulation of thrombin-activated receptor signaling can contribute to pathological conditions, including thrombosis, atherosclerosis, and inflammation. This pathway is a target for therapeutic interventions, with PAR inhibitors showing potential for treating various cardiovascular diseases and inflammatory disorders.'
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Proteins (4)

Compounds (23)