Serine Proteases and Their Serpin Inhibitors in the Nervous System

MATERIALS AND METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330 RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335 SEcnON VI: THE MARATEA CONFERENCE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 PHOTO LAYOUT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339 PARTICIPANTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 INDEX . . . . . . . . . . . . . . . . . . . ·. ··. ······························ 345 xxv SECTION I Biochemistry and cell biology of serine proteases and serpins THROMBIN STRUCIURAL REGIONS IN DETERMINING BIOREGULATORY FUNCTIONS JOHN W. FENTON n Wadsworth Center for Laboratories & Research, New York State Department of Health, Empire State Plaza, Box 509, Albany, NY 12201, and Department of Physiology, The Albany Medical College of Union University, Albany, NY 12208, USA INTRODUCTION Thrombin (EC 3. 4. 21. 5) is the activation product of its blood-circulating or cellular-sequestered zymogen, prothrombin. Unlike the majority of enzymes and activated proteins of the blood-coagulation, fibrinolytic, and complement systems, thrombin has multiple bioregulatory functions, which are central in hemostasis, wound 1 6 healing, and perhaps developmental, as well as certain disease processes. - Hemostasis occurs at three levels, which are: i) plasma proteins (e. g. , coagulation factors V, VIII, and IX; proteins C and S, complement components), ii) blood cells (e. g. , platelets, monocytes, neutrophils), and iii) blood vessels (e. g. , endothelium, smooth muscles). Moreover, thrombin functions at all three levels of hemostasis, while the majority of cell types known are responsive to greater or lesser extents to thrombin. Thrombin furthermore functions both as a proteolytic enzyme with arginine- or lysine-directed specificities or as a nonenzymic activated protein 1 6 (hormone-like) involving receptor occupancy on certain cells.

Klappentext

Proceedings of a NATO ARW held in Maratea, Italy, July 2-8, 1989

Zusammenfassung
Proceedings of a NATO ARW held in Maratea, Italy, July 2-8, 1989

Inhalt
Section I: Biochemistry and Cell Biology of Serine Proteases and Serpins.- 1: Thrombin Structural Regions in Determining Bioregutatory Functions.- 2: Regulation and Control of the Fibrinolytic System.- 3: A Key Molecule Dictating and Regulating Surface Plasmin Formation: The Receptor for Urokinase Plasminogen Activator.- 4: Regulation of Tissue Plasminogen Activator Secretion from Human Endothelial Cells.- 5: Thrombin Disintegrates Cell Surface Urokinase Focal Adhesion Plaques and Decreases Cell Extension: Implications for Axonal Growth.- 6: Structure and Function of Tissue-Type Plasminogen Activator.- 7: The Heparin Binding Site and Activation of Protease Nexin I.- 8: Polypeptide Chain Structure of Inter-?-Trypsin Inhibitor and Pre-?-Trypsin Inhibttor: Evidence for Chain Assembly by Glycan and Comparison with Other Kunin-Containing Proteins.- 9: Regulation of Protease Nexin I Activity and Target Protease Specificity by the Extracellular Matrix.- Section II: Molecular Biology of Serine Proteases and Serpins.- 10: Induction of the Urokinase-Type Plasminogen Activator Gene by Cytoskeeton-Disrupting Agents.- 11: Use of Protein Chemistry and Molecular Biology to Determine Interaction Areas Between Proteases and Their Inhibitors: The Thrombin-Hirudin Interaction as an Example.- 12: Signal Transduction Chains Involved in the Control of the Fibrinolytic Enzyme Cascade.- 13: Rodent Serpins: Accelerated Evolution and Novel Specificities.- 14: Structure of the Human Protease Nexin Gene and Expression of Recombinant forms of PNI.- 15: Evolutionary Adaptations of Serpins and Their Use in Designing New Proteinase Inhibitors.- Section III: Serine Proteases in the Nervous System.- 16: Plasminogen Activator in the Developing Nervous System.- 17: Multiple Roles for PlasminogenActivator System in Nervous System Development.- 18: Interaction of Plasminogen Activators with the Neuronal Surface.- 19: Glial Plasminogen Activators in Developing and Regenerating Neural Tissue.- 20: Plasminogen Activators in Development, Injury and Pathology of the Neuromuscular System.- 21: Relationship Between Plasminogen Activators and Regeneration Capacities of Rat Skeletal Muscle.- Section IV: Balance of Proteases and Serpins in the Nervous System.- 22: A Cascade Approach to Synapse Formation Based on Thrombogenic and Fibrinolytic Models.- 23: Localized Extracellular Proteolysis May Convey Inductive Signals Between Nerve and Muscle Cells During Synaptogenesis.- 24: Steps in Establishing a Biological Relevance for Gliaderived Nexin.- Section V: Serpins in Degenerative and Malignant Neurologic Diseases.- 25: Protease Inhibitors in Neurologic Diseases.- 26: Presence and Significance of ?1-Antitrypsin in Human Brain Tumors.- 27: Serpins and Brain Tumors: Roles in Pathogenesis.- 28: A Serine Protease Inhibitor Domain Encoded Within the Alzheimer Disease Associated Amyloid ?-Protein Precursor Gene.- 29: The Serpin, al-Antichymotrypsin, in Brain Aging and Diseases of The Nervous System.- 30: Protease Nexin I Immunostaining in Alzheimer's Disease.- Section VI: The Maratea Conference.- Photo Layout.- Participants.