Proceedings of an International Symposium held in Chapel Hill, North Carolina, April 13-16, 1996

Springer Book Archives

I. Introduction.- 1. Serpins: From the Way It Was to the Way It Is.- 2. Serpins: A Mechanistic Class of Their Own.- II. Coagulation.- 3. Antithrombin: A Bloody Important Serpin.- 4. Heparin Cofactor II.- 5. PCI: Protein C Inhibitor?.- 6. Molecular Basis for the Resistance of Fibrin-Bound Thrombin to Inactivation by Heparin/Serpin Complexes.- III. Neurobiology and Cancer.- 7. Regulation of Neurons and Astrocytes by Thrombin and Protease Nexin-1: Relationship to Brain Injury.- 8. Maspin: A Tumor Suppressing Serpin.- 9. Proteases and Protease Inhibitors in Tumor Progression.- IV. Fibrinolysis.- 10. The Role of Reactive-Center Loop Mobility in the Serpin Inhibitory Mechanism.- 11. Substrate Specificity of Tissue Type Plasminogen Activator.- 12. Plasminogen Activator Inhibitor Type-2: A Spontaneously Polymerizing Serpin that Exists in Two Topological Forms.- 13. Of Mice and Men: The Function of Plasminogen Activator Inhibitors (PAIs) in Vivo.- V. Development and Reproduction.- 14. Biology of Progesterone-Induced Uterine Serpins.- 15. Serpins from an Insect, Manduca sexta.- 16. The Significance of Serpins in the Regulation of Proteases in the Male Genital Tract.- VI. Inflammation.- 17. Serpins and Programmed Cell Death.- 18. C 1 Inhibitor: Functional Analysis of Naturally-Occurring Mutant Proteins.- 19. Serp-1, a Poxvirus-Encoded Serpin, Is Expressed as a Secreted Glycoprotein that Inhibits the Inflammatory Response to Myxoma Virus Infection.- 20. Dysfunctional Variants and the Structural Biology of the Serpins.- VI. Noninhibitor Serpins.- 21. Structure-Function Studies on PEDF: A Noninhibitory Serpin with Neurotrophic Activity.- 22. Colligin, a Collagen Binding Serpin.- VII. Abstracts.- Coagulation, Neurobiology, and Cancer.- Fibrinolysis, Development, and Reproduction.- Inflammation and Noninhibitor Serpins.- Contributors.

Serpins (serine protease inhibitors) are a superfamily of proteins whose physiologi cal action is primarily targeted to inhibiting serine proteases. There are instances where serpins are not inhibitors (and can carry steroid hormones for instance), yet key structural and functional elements found in all serpins are maintained in these 'non-inhibitor' ser pins. Many serpins have well-described biological properties which influence pathophysi ological events, including: antithrombin (historically called antithrombin III), ai-protease inhibitor (historically called ai-antitrypsin), and plasminogen activator inhibitor-I, just to mention a few. A deficiency or defect in antithrombin leads to venous thromboembolic disease, while a deficiency or defect in ai-protease inhibitor is associated with chronic obstructive pulmonary emphysema. In contrast, it has been suggested that increased levels of plasminogen activator inhibitor-l may be a predisposition to myocardial infarction. The list goes on for each of our own "favorite" serpin. The biological roles found for serpins are key participants in almost every physiological event. In other words, serine proteases are needed for many events in biology and the role of serpins to down regulate these pro teases is essential. Thus, just using these three examples above for serpins and their patho physiological roles reminds us that the medical costs to control such events is significant worldwide.