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.
Targeting the PARs- 2.8. Summary- 2.9. Acknowledgements- 2.10. References- 3. Regulation of thrombin receptor signaling- 3.1. Introduction- 3.2. Cell type specific expression of thrombin receptors3.3. Thrombin receptor activation and signaling- 3.3.1. Proteolytic mechanism of thrombin receptor activation- 3.3.2. Thrombin receptor signaling to heterotrimeric G-proteins- 3.3.3. Cell type specific thrombin receptor signaling- 3.4. Regulation of thrombin receptor signaling- 3.4.1. Thrombin receptor desensitization- 3.4.2. Thrombin receptor internalization- 3.4.3. Thrombin receptor down-regulation- 3.5. PAR activation and signaling by other proteases- 3.6. Conclusions- 3.7. Acknowledgements- 3.8. References- 4. Thrombin-activated protein C: integrated to regulate vascular physiology- 4.1. The protein C pathway is localized to the endothelial cell surface and limits thrombin generation through negative feedback- 4.2. APC has protective effects in systemic inflammation that are independent of its anticoagulant function- 4.3. The thrombin receptor PAR1 mediates APC signaling in tissues culture- 4.4. APC and thrombin can mediate opposite cellular responses in endothelial cells through PAR1 activation4.4.1. Barrier integrity- 4.4.2. Adhesion molecule expression- 4.4.3. Apoptosis- 4.5. Role of the sphingosine-1 phosphate pathway in mediating protective signaling by PAR1. - 4.6. Protective PAR1 signaling by APC is mechanistically coupled to PC activation by thrombin- 4.7. Not PAR1- or EPCR-dependent mechanisms for signaling by the PC pathway?- 4.8. Thrombin-PAR1 and APC-PAR1 signaling in in vivo models of inflammation - 4.9. How can activation of the thrombin receptor PAR1 by the PC pathway be of physiological relevance?... EAN/ISBN : 9780387096377 Publisher(s): Springer, Berlin, Springer, New York Discussed keywords: Thrombin Format: ePub/PDF
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