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Molecular mechanisms regulating Proteinase‐Activated Receptors (PARs)
Author(s) -
Chandrabalan Arundhasa,
Ramachandran Rithwik
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15829
Subject(s) - receptor , effector , biology , g protein coupled receptor , signal transduction , mechanism (biology) , protease activated receptor , function (biology) , proteolytic enzymes , microbiology and biotechnology , neuroscience , enzyme , platelet , immunology , biochemistry , thrombin , philosophy , epistemology
Proteinase‐activated receptors (PARs) are a four‐member family of G protein‐coupled receptors defined by their irreversible proteolytic mechanism of activation. PARs have emerged as important regulators of various physiological responses and are implicated in numerous pathological conditions. Importantly, PAR1 and PAR4 are critical regulators of platelet function, while PAR2 is well established as a driver of inflammatory responses. PAR‐targeted drug development efforts are therefore of great interest. In this review, we provide an overview of recent advances in our understanding of molecular mechanisms underlying PAR activation, effector interaction, and signaling. We also provide an overview of the diverse proteolytic enzymes that are now established as PAR regulators and describe the ability of different enzymes to elicit biased signaling through PARs. Finally, we highlight recent advances in the development of PAR‐targeted pharmacological agents and discuss recent structure–activity relationship studies.