The biological role of protease-activated receptors in angiology. The present view.
The mechanism of initiation and growth of a thrombus in atherosclerotic arteries, although investigated extensively, has not been sufficiently elucidated. Understanding the molecular mechanisms that lead to stroke, unstable angina and myocardial infarction is of paramount importance. Protease-activated receptors (PARs) belong to a recently discovered and so far not fully characterized family of transmembrane proteins, which are involved in the initiation growth of thrombi in atherosclerotic arteries. PARs are a G-protein-coupled family of receptors which mediate a cellular function with the aid of enzymes. All of them have identical structural organization and are activated by a very similar mechanism. The enzyme (serine protease) cleaves an extracellular amino-terminal fragment of the receptor in order to unmask a new amino-terminal, 5-6 residues of which serve as the tethering ligand, able to activate its maternal receptor. According to the most recently published reports, in eukaryotic organisms there are 5 different PARs: from PAR 1 to PAR 4 found in human organisms and PAR 5 discovered as a 14-3-3 protein, identified firstly in C. elegans and Drosophila melanogaster. Up to now numerous experiments have been conducted with the aim to understand more precisely the mechanisms of PARs activation and activity. The present paper summarizes the most important and most recently published reports concerning this problem, which seems to be most relevant in angiology.
Skórkowska
K
K
Department of Angiology, Diabetology and Hypertension Medical University, Wroclaw, Poland. cath-cor@poczta.onet.pl
Adamiec
R
R
D056649:Cathepsin G; D002403:Cathepsins / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology; D015539:Platelet Activation / Q000502:physiology; D044463:Receptor, PAR-1 / Q000502:physiology; D044464:Receptor, PAR-2 / Q000502:physiology; D044462:Receptors, Proteinase-Activated / Q000502:physiology*; D012697:Serine Endopeptidases / Q000502:physiology; D013917:Thrombin / Q000032:analysis / Q000502:physiology
D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D044462:Receptors, Proteinase-Activated; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D013917:Thrombin