Protease activated receptors in cardiovascular function and disease

Junor A. Barnes, Shamjeet Singh, Aldrin V Gomes

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Recent studies have shown that a novel class of protease activated receptors (PARs), which are composed of seven transmembrane G protein-coupled domains, are activated by serine proteases such as thrombin, trypsin and tryptase. Although four types (PAR 1, PAR 2, PAR 3 and PAR 4) of this class of receptors have been identified, their discrete physiological and pathological roles are still being unraveled. Extracellular proteolytic activation of PARs results in the cleavage of specific sites in the extracellular domain and formation of a new N-terminus which functions as a tethered ligand. The newly formed tethered ligand binds intramolecularly to an exposed site in the second transmembrane loop and triggers G-protein binding and intracellular signaling. Recent studies have shown that PAR-1, PAR-2 and PAR-4 have been involved in vascular development and a variety of other biological processes including apoptosis and remodeling. The use of animal model systems, mainly transgenic mice and synthetic tethered ligand domains, have contributed enormously to our knowledge of molecular signaling and the regulatory properties of various PARs in cardiomyocytes. This review focuses on the role of PARs in cardiovascular function and disease.

Original languageEnglish (US)
Pages (from-to)227-239
Number of pages13
JournalMolecular and Cellular Biochemistry
Volume263
Issue number1
DOIs
StatePublished - Aug 2004
Externally publishedYes

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Keywords

  • Cardiovascular disease
  • Protease activated receptor
  • Thrombin

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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