Plasminogen: Structure, Activation, and Regulation

I. Plasminogen: Structure and Regulation.- 1. Human Plasminogen: Structure, Activation, and Function.- 1. Introduction.- 2. Structure of Human Plasminogen.- 2.1. Primary Protein Structure.- 2.2. Gene Organization.- 3. Activation of Human Plasminogen.- 3.1. Activation by Physiological Activators.- 3.1.1. Urokinase-type Plasminogen Activator.- 3.1.2. Tissue-type Plasminogen Activator.- 3.2. Activation by Bacterial-derived Plasminogen Activators.- 3.2.1. Streptokinase.- 3.2.2. Staphylokinase.- 4. Targets for Plasmin Activity.- 5. Dysplasminogenemias and Phenotypic Manifestations.- 6. Conclusions.- References.- 2. Plasminogen Activators: Structure and Function.- 1. Introduction.- 2. Serine Proteases.- 3. Urokinase Plasminogen Activator, uPA.- 3.1. Serine Protease Domain.- 3.2. N-terminal Domains.- 3.2.1. KR Module.- 3.2.2. EG Module.- 4. Mechanisms Regulating uPA Function.- 4.1. Zymogen Activation.- 4.2. Zymogen Activity.- 4.3. Reciprocal Zymogen Activation.- 4.4. uPAR Stimulation of Plasminogen Activation.- 4.4.1. uPA and the Template Mechanism.- 4.4.2. Plasminogen and the Template Mechanism.- 4.5. Avian uPA, a Special Case?.- 5. Tissue Plasminogen Activator, tPA.- 5.1. Serine Protease Domain.- 5.2. N-terminal Domains.- 5.2.1. KR Modules.- 5.2.2. Fl-EG Supermodule.- 6. Mechanisms Regulating tPA Function.- 6.1. Zymogenicity.- 6.2. Fibrin Stimulation of Plasminogen Activation.- 6.2.1. tPA/fibrin Interaction.- 6.2.2. Vampire Bat Plasminogen Activator.- 6.3. Cellular Mechanisms Regulating tPA Activity.- 6.3.1. Endothelial Cells.- 6.3.2. Vascular Smooth Muscle Cells.- 6.3.3. Prion Protein.- 7. Concluding Remarks.- References.- 3. Plasminogen Activators Inhibitors.- 1. Plasminogen Activator Inhibitor-1.- 1.1. Natural and Recombinant PAI-1.- 1.2. Distinct Conformations of PAI-1.- 1.3. Target Specificity of PAI-1.- 1.4. PAI-1 in Patho-Physiological Processes.- 1.4.1. PAI-1 and Cardiovascular Disease.- 1.4.2. PAI-1 and Cancer.- 1.5. PAI-1 Inhibitors and their Binding Sites.- 2. Plasminogen Activator Inhibitor-2.- 2.1. Function of PAI-2.- 2.2. PAI-2 Polymerization.- 3. Plasminogen Activator Inhibitor-3.- 3.1. Target Specificity of PAJ-3.- 3.2. Physiological Role of PAI-3.- References.- 4. Regulation of Plasminogen Gene Expression.- 1. Introduction.- 2. The Plasminogen Gene.- 2.1. Mechanisms of Constitutive Regulation of Plasminogen Gene Expression.- 2.2. Plasminogen Distribution in Tissues.- 3. Regulation of Plasminogen Gene Expression in vitro and in vivo.- 3.1. Interleukin-6.- 3.2. Glucocorticoids.- 3.3. LPS.- 3.4. Tumor Necrosis Factor-? (TNF-?) and Transforming Growth Factor-? (TGF-?).- 3.5. Interleukin-1.- 3.6. Kainic Acid.- 4. Conclusions.- Acknowledgments.- References.- 5. Plasminogen Receptors.- 1. Introduction to Cellular Plasminogen Activation.- 2. Mechanism of Cellular Plasminogen Binding.- 2.1. History.- 2.2. Kinetics of Plasminogen Binding.- 2.3. Binding of Plasminogen Isoforms.- 3. Plasminogen Receptors as Regulators of Plasmin Activity.- 4. Modulation of Receptor Expression.- 4.1. Plasminogen Receptor Expression on Platelets.- 4.2. Plasminogen Receptor Expression on Endothelial Cells.- 4.3. Plasminogen Receptor Expression on Peripheral Blood Cells.- 4.4. Plasminogen Receptor Expression on Tumor Cells.- 5. Candidate Plasminogen Receptors.- 6. Annexin II, P11, and Annexin II Heterotetramer as Candidate Plasminogen Receptors.- 7. Concluding Remarks.- References.- 6. The Role of Lys-Plasminogen in Cell-Mediated Plasmin Production.- 1. Introduction.- 2. Key Differences between Glu-Plasminogen and Lys-Plasminogen.- 3. Mechanisms by which Plasminogen Activation is Enhanced on the Cell Surface.- 3.1. Role of the Glu-Plasminogen to Lys-Plasminogen Conversion in Plasminogen Activation by t-PA on the Cell Surface.- 3.2. Role of the Glu-Plasminogen to Lys-Plasminogen Conversion in Plasminogen Activation by u-PA on the Cell Surface.- 3.3. Effect of Cells on Conversion of [D(646)E]Glu-Pg to [D(646)E]Lys-Pg by Exogenous Plasmin.- 4. Co