Proteinase-activated receptor 1 (PAR-1) and cell apoptosis.
This review summarizes the main aspects and newest findings of how proteinase-activated receptor 1 (PAR-1) may modulate programmed cell death. Activation of PAR-1 has been found to induce or inhibit apoptosis in a variety of cells, depending on the dosage of its physiological agonist thrombin, or that of synthetic receptor activators. To date, cellular targets for PAR-1-mediated effects on apoptosis include neuronal, endothelial, and epithelial cells, fibroblasts, and tumor cells. The signaling pathways involved in the induction or prevention of apoptosis by PAR-1 activation are diverse, and include JAK/STAT, RhoA, myosin light chain kinase, ERK1/2, and various Bcl-2 family members. In view of the well-established involvement of microbial proteinases in host tissue malfunction, the article also elaborates on the possible significance of PAR-1 activation for the pathogenesis of infectious disease.
Flynn
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Department of Biological Sciences and Mucosal Inflammation Research Group, The University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Buret
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D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D003141:Communicable Diseases / Q000209:etiology; D006801:Humans; D053614:Janus Kinase 2; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D018994:Myosin Light Chains / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D018994:Myosin Light Chains; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D044463:Receptor, PAR-1; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013917:Thrombin; D020742:rhoA GTP-Binding Protein