thrombin-activated receptor activity

Definition

Target type: molecularfunction

A G protein-coupled receptor activity that is activated by cleavage by thrombin, which exposes a tethered ligand corresponding to the new N-terminus, which binds to the receptor and activates it. [GOC:ai, GOC:pg, PMID:20423334]

Thrombin-activated receptor (PAR) activity involves a complex cascade of molecular events that ultimately lead to cellular signaling and various physiological responses. PARs are G protein-coupled receptors (GPCRs) that are activated by proteolytic cleavage of their N-terminal extracellular domain. Thrombin, a serine protease, is a key activator of PARs, particularly PAR1 and PAR4.

Upon thrombin cleavage, the newly exposed N-terminus of the PAR acts as a tethered ligand, binding to the receptor's extracellular domain and initiating signaling. This interaction triggers a conformational change in the receptor, leading to the activation of intracellular signaling pathways.

The activation of PARs by thrombin can initiate a variety of downstream events, including:

- **G protein activation:** PARs couple to heterotrimeric G proteins, primarily Gq and Gi. The activation of Gq leads to the activation of phospholipase C (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 promotes calcium release from intracellular stores, while DAG activates protein kinase C (PKC).
- **MAP kinase signaling:** PAR activation can activate the mitogen-activated protein kinase (MAPK) signaling pathway, leading to the phosphorylation of various downstream targets involved in cell proliferation, differentiation, and survival.
- **Calcium signaling:** The release of calcium from intracellular stores, triggered by IP3, plays a critical role in a wide range of cellular processes, including muscle contraction, secretion, and gene expression.
- **Cytoskeletal rearrangement:** PAR activation can induce changes in the cytoskeleton, leading to cell migration, adhesion, and wound healing.
- **Transcriptional regulation:** PARs can regulate gene expression by influencing the activity of transcription factors, affecting the synthesis of proteins involved in various cellular functions.

In summary, thrombin-activated receptor activity is a multifaceted process that involves the proteolytic cleavage of PARs, leading to the activation of G proteins, calcium signaling, MAP kinase signaling, and cytoskeletal rearrangement. These events ultimately result in a diverse range of physiological responses, including platelet aggregation, smooth muscle contraction, inflammation, and tissue repair.'
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Proteins (3)

Compounds (18)