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PAR2: The Cornerstone of Pancreatic Diseases

P. Suhaj, T. Olejar, R. Matej

. 2022 ; 71 (5) : 583-596. [pub] 20220908

Language English Country Czech Republic

Document type Review, Journal Article

Persistent link   https://www.medvik.cz/link/bmc22029552

It has been 30 years since the first member of the protease-activated receptor (PAR) family was discovered. This was followed by the discovery of three other receptors, including PAR2. PAR2 is a G protein-coupled receptor activated by trypsin site-specific proteolysis. The process starts with serine proteases acting between arginine and serine, creating an N-terminus that functions as a tethered ligand that binds, after a conformational change, to the second extracellular loop of the receptor, leading to activation of G-proteins. The physiological and pathological functions of this ubiquitous receptor are still elusive. This review focuses on PAR2 activation and its distribution under physiological and pathological conditions, with a particular focus on the pancreas, a significant producer of trypsin, which is the prototype activator of the receptor. The role in acute or chronic pancreatitis, pancreatic cancer, and diabetes mellitus will be highlighted.

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$a It has been 30 years since the first member of the protease-activated receptor (PAR) family was discovered. This was followed by the discovery of three other receptors, including PAR2. PAR2 is a G protein-coupled receptor activated by trypsin site-specific proteolysis. The process starts with serine proteases acting between arginine and serine, creating an N-terminus that functions as a tethered ligand that binds, after a conformational change, to the second extracellular loop of the receptor, leading to activation of G-proteins. The physiological and pathological functions of this ubiquitous receptor are still elusive. This review focuses on PAR2 activation and its distribution under physiological and pathological conditions, with a particular focus on the pancreas, a significant producer of trypsin, which is the prototype activator of the receptor. The role in acute or chronic pancreatitis, pancreatic cancer, and diabetes mellitus will be highlighted.
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