Thrombin
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Table of contents- 1. Thrombin: structure, functions and regulation- 1.1. Introduction- 1.2. Thrombin and Na+- 1.3. Thrombin structure- 1.4. Kinetics of Na+ activation- 1.5. Structures of E , E and E:Na+- 1.6. Thrombin interaction with protein C- 1.7. Thrombin interaction with the PARs- 1.8. Dissociating procoagulant and anticoagulant activities- 1.9. WE: a prototypic anticoagulant/antithrombotic thrombin1.10. References - 2. Thrombin: to PAR or not to PAR, and the regulation of inflammation- 2.1. Introduction- 2.2. Thrombin and the search for its receptor- 2.3. Enzymes other than thrombin that are potential physiological regulators of PARs- 2.3.1. Enzymes of the coagulation pathway- 2.3.2. Proteinases of the gastrointestinal tract- 2.3.3. PAR-regulating proteinases in the central nervous system2.3.4. Immune cell-derived proteinases and PARs- 2.3.5. Tumor-derived proteinases and a possible physiological role for kallikrein-related peptidases (KLKs) as PAR regulators- 2.3.6. Pathogen-derived proteinases and PAR activation- 2.4. Receptor dynamics and cell signaling: enzyme versus peptide-mediated activation- 2.4.1. PAR-mediated signaling- 2.4.2. PAR activation by enzyme versus peptide- 2.5. PAR activation and the inflammation actions of thrombin - 2.6. Non-PAR mechanisms of cell regulation mediated by thrombin and other proteinases - 2.6.1. Signaling targets that are not "classical" receptors- 2.6.2. Non-catalytic mechanisms for proteinase-mediated signaling- 2.6.3. Thrombin-mediated generation of agonists from fibrin and other substrates- 2.7. Therapeutic implications of thrombin action via PAR and non-PAR mechanisms- 2.7.1. Targeting thrombin and other serine proteinases- 2.7.2.