Proteolytic Enzymes and Cell Signaling: Pharmacological Lessons

摘要: The innate immune response to invading organisms or inflammatory injury involves the activation of proteolytic enzyme cascades that in turn trigger host defense signaling pathways. Although it has been known for over 40 years proteinases such as thrombin, trypsin, and chymotrypsin can hormone-like signal transduction pathways target tissues, mechanisms have only recently come into focus. Thus, enzymes coagulation cascade (thrombin, factor VIIa/Xa, activated protein C) are now cells by cleaving activating so-called proteinase-activated receptors (PARs). This cleavage unmasks a PAR “tethered ligand” sequence triggers receptor signaling. Not endogenous activate PARs unmasking “TL” sequence, but they also “disarm” Receptor “disarming” results from removing TL entirely, thus preventing its subsequent other proteinases. chapter provides an overview multiple whereby affect tissue function. emphasizes key role “pharmacological approach” using PAR-activating peptides, antagonists, bioassays responses both vitro vivo employing receptor-null mice (PAR1−/−/PAR2−/−) played providing insight physiological roles play mediators inflammation pain.