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The Molecular Basis for Anti-Proteolytic and Non-Proteolytic Functions of Plasminogen Activator Inhibitor Type-1: Roles of the Reactive Centre Loop, the Shutter Region, the Flexible Joint Region and the Small Serpin Fragment
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Troels Wind
Veröffentlicht/Copyright:
1. Juni 2005
Abstract
The serine proteinase inhibitor plasminogen activator inhibitor type-1 (PAI-1) is the primary physiological inhibitor of the tissuetype and the urokinasetype plasminogen activator (tPA and uPA, respectively) and as such an important regulator of proteolytic events taking place in the circulation and in the extracellular matrix. Moreover, a few nonproteolytic functions have been ascribed to PAI-1, mediated by its interaction with vitronectin or the interaction between the uPAPAI-1 complex bound to the uPA receptor and members of the low density lipoprotein receptor family. PAI-1 belongs to the serpin family, characterised by an unusual conformational flexibility, which governs its molecular interactions. In this review we describe the antiproteolytic and nonproteolytic functions of PAI-1 from both a biological and a biochemical point of view. We will relate the various biological roles of PAI-1 to its biochemistry in general and to the different conformations of PAI-1 in particular. We put emphasis on the intramolecular rearrangements of PAI-1 that are required for its antiproteolytic as well as its nonproteolytic functions.
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Published Online: 2005-06-01
Published in Print: 2002-01-23
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
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Artikel in diesem Heft
- Non-Enzymatic Activities of Proteases: From Scepticism to Reality
- The Urokinase Plasminogen Activator Receptor in the Regulation of the Actin Cytoskeleton and Cell Motility
- The Molecular Basis for Anti-Proteolytic and Non-Proteolytic Functions of Plasminogen Activator Inhibitor Type-1: Roles of the Reactive Centre Loop, the Shutter Region, the Flexible Joint Region and the Small Serpin Fragment
- Nervous System Pathology: The Fibrin Perspective
- Post-Transcriptional Regulation of Gene Expression in the Plasminogen Activation System
- Role of Myofibroblasts at the Invasion Front
- Transmodulation of Cell Surface Regulatory Molecules via Ectodomain Shedding
- The Plasminogen Activating System in Periodontal Health and Disease
- Apolipoprotein(a): Structure-Function Relationship at the Lysine-Binding Site and Plasminogen Activator Cleavage Site
- Anti-Invasive Effects of Green Tea Polyphenol EpiGalloCatechin-3-Gallate (EGCG), a Natural Inhibitor of Metallo and Serine Proteases
- Inhibition of Receptor-Dependent Urokinase Signaling by Specific Ser to Glu Substitutions
- Activation of p38 MAP-Kinase and Caldesmon Phosphorylation Are Essential for Urokinase-Induced Human Smooth Muscle Cell Migration
- Growth Factor-Dependent Proliferation and Invasion of Muscle Satellite Cells Require the Cell-Associated Fibrinolytic System
- The Col-1 Module of Human Matrix Metalloproteinase-2 (MMP-2): Structural/Functional Relatedness between Gelatin-Binding Fibronectin Type II Modules and Lysine-Binding Kringle Domains
- Random Peptide Bacteriophage Display as a Probe for Urokinase Receptor Ligands
- Plasmin Produces an E-Cadherin Fragment That Stimulates Cancer Cell Invasion
- The Role of Proteases in Fibronectin Matrix Remodeling in Thyroid Epithelial Cell Monolayer Cultures
- Induction of Fibronectin mRNA by Urokinase- and Tissue-Type Plasminogen Activator in Human Skin Fibroblasts: Differential Role of u-PA and t-PA at the Fibronectin Protein Level
- Platelet Activating Factor Inhibits the Expression of Matrix Metalloproteinases and Affects Invasiveness and Differentiation in a System of Human Neuroblastoma Clones
- UVA Light Stimulates the Production of Cathepsin G and Elastase-Like Enzymes by Dermal Fibroblasts: A Possible Contribution to the Remodeling of Elastotic Areas in Sun-Damaged Skin
- uPA-Silica-Particles (SP-uPA): A Novel Analytical System to Investigate uPA-uPAR Interaction and to Test Synthetic uPAR Antagonists as Potential Cancer Therapeutics
- Monocyte-Expressed Urokinase Regulates Human Vascular Smooth Muscle Cell Migration in a Coculture Model
- Distinct Expression Pattern of Two Related Human Proteins Containing Multiple Types of Protease-Inhibitory Modules
- Osteopontin Modulates Prostate Carcinoma Invasive Capacity through RGD-Dependent Upregulation of Plasminogen Activators
- Expression of Matrix Metalloproteases (MMP-2, MT1-MMP) and Their Tissue Inhibitor (TIMP-2) by Rat Sertoli Cells in Culture: Implications for Spermatogenesis
Artikel in diesem Heft
- Non-Enzymatic Activities of Proteases: From Scepticism to Reality
- The Urokinase Plasminogen Activator Receptor in the Regulation of the Actin Cytoskeleton and Cell Motility
- The Molecular Basis for Anti-Proteolytic and Non-Proteolytic Functions of Plasminogen Activator Inhibitor Type-1: Roles of the Reactive Centre Loop, the Shutter Region, the Flexible Joint Region and the Small Serpin Fragment
- Nervous System Pathology: The Fibrin Perspective
- Post-Transcriptional Regulation of Gene Expression in the Plasminogen Activation System
- Role of Myofibroblasts at the Invasion Front
- Transmodulation of Cell Surface Regulatory Molecules via Ectodomain Shedding
- The Plasminogen Activating System in Periodontal Health and Disease
- Apolipoprotein(a): Structure-Function Relationship at the Lysine-Binding Site and Plasminogen Activator Cleavage Site
- Anti-Invasive Effects of Green Tea Polyphenol EpiGalloCatechin-3-Gallate (EGCG), a Natural Inhibitor of Metallo and Serine Proteases
- Inhibition of Receptor-Dependent Urokinase Signaling by Specific Ser to Glu Substitutions
- Activation of p38 MAP-Kinase and Caldesmon Phosphorylation Are Essential for Urokinase-Induced Human Smooth Muscle Cell Migration
- Growth Factor-Dependent Proliferation and Invasion of Muscle Satellite Cells Require the Cell-Associated Fibrinolytic System
- The Col-1 Module of Human Matrix Metalloproteinase-2 (MMP-2): Structural/Functional Relatedness between Gelatin-Binding Fibronectin Type II Modules and Lysine-Binding Kringle Domains
- Random Peptide Bacteriophage Display as a Probe for Urokinase Receptor Ligands
- Plasmin Produces an E-Cadherin Fragment That Stimulates Cancer Cell Invasion
- The Role of Proteases in Fibronectin Matrix Remodeling in Thyroid Epithelial Cell Monolayer Cultures
- Induction of Fibronectin mRNA by Urokinase- and Tissue-Type Plasminogen Activator in Human Skin Fibroblasts: Differential Role of u-PA and t-PA at the Fibronectin Protein Level
- Platelet Activating Factor Inhibits the Expression of Matrix Metalloproteinases and Affects Invasiveness and Differentiation in a System of Human Neuroblastoma Clones
- UVA Light Stimulates the Production of Cathepsin G and Elastase-Like Enzymes by Dermal Fibroblasts: A Possible Contribution to the Remodeling of Elastotic Areas in Sun-Damaged Skin
- uPA-Silica-Particles (SP-uPA): A Novel Analytical System to Investigate uPA-uPAR Interaction and to Test Synthetic uPAR Antagonists as Potential Cancer Therapeutics
- Monocyte-Expressed Urokinase Regulates Human Vascular Smooth Muscle Cell Migration in a Coculture Model
- Distinct Expression Pattern of Two Related Human Proteins Containing Multiple Types of Protease-Inhibitory Modules
- Osteopontin Modulates Prostate Carcinoma Invasive Capacity through RGD-Dependent Upregulation of Plasminogen Activators
- Expression of Matrix Metalloproteases (MMP-2, MT1-MMP) and Their Tissue Inhibitor (TIMP-2) by Rat Sertoli Cells in Culture: Implications for Spermatogenesis
