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Proteinase‐activated receptors: Tethered ligands and receptor‐activating peptides
Author(s) -
Hollenberg Morley D.
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10301
Subject(s) - receptor , proteolysis , g protein coupled receptor , protease activated receptor , biochemistry , ligand (biochemistry) , microbiology and biotechnology , chemistry , enzyme linked receptor , peptide sequence , signal transduction , 5 ht5a receptor , extracellular , biology , functional selectivity , enzyme , immunology , platelet , gene , thrombin
Proteinase‐activated receptors (PARs), newly‐discovered members of the G‐protein‐coupled receptor superfamily, comprising four cloned family members (PARs 1 to 4), are activated by the proteolytic unmasking of a “tethered ligand” sequence situated in the N‐terminal extracellular receptor domain. Furthermore, synthetic peptides with sequences based on the revealed tethered ligands can, in the absence of proteolysis, trigger receptor signaling. This report reviews the data supporting the tethered ligand mechanism of receptor activation, outlines the utility of the receptor‐activating peptides (so‐called PAR‐APs) for exploring the potential physiological roles of the PARs, and discusses the potential differences between the activation of the receptors via their tethered ligands as opposed to activation by the soluble peptides having the same amino acid sequences. Drug Dev. Res. 59:336–343, 2003. © 2003 Wiley‐Liss, Inc.