Proteinase-activated receptors: novel mechanisms of signaling by serine proteases

Am J Physiol. 1998 Jun;274(6):C1429-52. doi: 10.1152/ajpcell.1998.274.6.C1429.


Although serine proteases are usually considered to act principally as degradative enzymes, certain proteases are signaling molecules that specifically regulate cells by cleaving and triggering members of a new family of proteinase-activated receptors (PARs). There are three members of this family, PAR-1 and PAR-3, which are receptors for thrombin, and PAR-2, a receptor for trypsin and mast cell tryptase. Proteases cleave within the extracellular NH2-terminus of their receptors to expose a new NH2-terminus. Specific residues within this tethered ligand domain interact with extracellular domains of the cleaved receptor, resulting in activation. In common with many G protein-coupled receptors, PARs couple to multiple G proteins and thereby activate many parallel mechanisms of signal transduction. PARs are expressed in multiple tissues by a wide variety of cells, where they are involved in several pathophysiological processes, including growth and development, mitogenesis, and inflammation. Because the cleaved receptor is physically coupled to its agonist, efficient mechanisms exist to terminate signaling and prevent uncontrolled stimulation. These include cleavage of the tethered ligand, receptor phosphorylation and uncoupling from G proteins, and endocytosis and lysosomal degradation of activated receptors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA-Binding Proteins / physiology*
  • GTP-Binding Proteins / metabolism
  • Humans
  • Molecular Sequence Data
  • Protein Binding / physiology
  • Receptor, PAR-2
  • Receptors, Cell Surface / agonists
  • Receptors, Cell Surface / physiology*
  • Receptors, Thrombin / agonists
  • Receptors, Thrombin / physiology*
  • Saccharomyces cerevisiae Proteins*
  • Serine Endopeptidases / physiology*
  • Signal Transduction*
  • Transcription Factors / physiology*


  • DNA-Binding Proteins
  • Receptor, PAR-2
  • Receptors, Cell Surface
  • Receptors, Thrombin
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • YAP1 protein, S cerevisiae
  • protease-activated receptor 3
  • Serine Endopeptidases
  • GTP-Binding Proteins