Department of Pathology and Molecular Medicine, Third Medical Faculty, Charles University and Thomayer University Hospital, Prague, Czech Republic. petr.suhaj@ftn.
Physiol Res. 2022 Nov 28;71(5):583-596. doi: 10.33549/physiolres.934931. Epub 2022 Sep 8.
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.
自发现第一个蛋白酶激活受体（PAR）家族成员以来，已经过去了 30 年。随后又发现了另外三个受体，包括 PAR2。PAR2 是一种 G 蛋白偶联受体，可被胰蛋白酶特异性蛋白水解激活。该过程始于丝氨酸蛋白酶在精氨酸和丝氨酸之间的作用，产生一个 N 端作为连接配体，在构象变化后与受体的第二个细胞外环结合，从而激活 G 蛋白。这个普遍存在的受体的生理和病理功能仍然难以捉摸。这篇综述重点介绍了 PAR2 的激活及其在生理和病理条件下的分布，特别关注了胰腺，胰腺是胰蛋白酶的重要产生者，也是该受体的原型激活剂。还将重点介绍其在急性或慢性胰腺炎、胰腺癌和糖尿病中的作用。
