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Proteinase‐activated receptor domains and signaling
Author(s) -
Hollenberg Morley D.,
Compton Steven J.
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.10302
Subject(s) - g protein coupled receptor , signal transduction , microbiology and biotechnology , receptor , biology , extracellular , intracellular , palmitoylation , phosphorylation , 5 ht5a receptor , g protein , g protein coupled receptor kinase , enzyme linked receptor , protease activated receptor , biochemistry , immunology , enzyme , thrombin , platelet , cysteine
Given that the proteinase‐activated receptors (PARs) are activated by a “tethered ligand mechanism,” an important question to answer is: Which other extracellular domains of the receptors are involved in this novel signaling mechanism? Further, as for other G‐protein‐coupled receptors (GPCRs), it is of importance to know about the intracellular receptor domains that are involved in coupling receptor activation to signal transduction. Studies summarized in this article have singled out the importance of extracellular loop‐2 of PAR 1 and PAR 2 for tethered‐ligand signaling. In human PAR 1 , but not in PAR 2 , a short sequence in the extracellular N‐terminal domain (Q 83 to G 94 ) is also important for receptor activation. As for other GPCRs, intracellular loops 2 and 3 mediate receptor‐G‐protein coupling, and the C‐terminal sequence, with a putative “palmitoylation” site and target residues for kinase C phosphorylation, plays a role in receptor signaling and desensitization. This article provides an overview of the experiments leading to the current understanding of the PAR domains involved in signal transduction. Drug Dev. Res. 59:344–349, 2003. © 2003 Wiley‐Liss, Inc.