Produktbild: Plasminogen: Structure, Activation, and Regulation

Plasminogen: Structure, Activation, and Regulation

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ISBN: 1461349494
ISBN 13: 9781461349495
Herausgeber: David M Waisman
Verlag: Springer Verlag GmbH
Umfang: xxi, 293 S.
Erscheinungsdatum: 17.09.2012
Auflage: 1/2012
Produktform: Kartoniert
Einband: Kartoniert

InhaltsangabeI. 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. Conclu

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Beschreibung

inthisresearchfieldandthemanyexcitingdiscoveriessuggeststhattheresearchefforts inthenextdecadewillrevealthemechanismsbywhichthecomponentsoftheplas­ minogensysteminteractandregulatebothplasminactivationandfunctionatacellular level. Plasminogen: Structure, activation, and regulationisdividedintotwosections. Thefirstsectiondealswiththestructureandregulationofplasminogen. Thechapters inthissectionrangefromdiscussionsofthestructureofplasminogenandtheregulation oftheplasminogengenetodiscussionsofthestructureandregulationofplasminogen activatorsandplasminogenactivatorinhibitors. Alsoexaminedistherelativelynewdata concerningthegenerationofanti-angiogenicmoleculesfromplasminogen. Thesecond sectiondealswiththephysiologicalandpathophysiologicalrolesofplasminogenaswell astheconsequencesofplasminogengeneknockout. Discussionsinthissectioninclude examinationoftheroleofplasminogeninhematopoieticmalignancies,tumorcell progression,angiogenesis,mammaryglandinvolution,woundhealing,andbone readsorption. xi xii Preface Inclosing,Iwouldliketothankmyadministrativeassistant,Ms. ViSommerfeld,for herinvaluableassistanceandtimelesseffortswiththeorganizationandeditingofthebook. Lastly,Iwouldliketoacknowledgetheeffortsoftheauthorsoftheindividualchapters, whoareauthorities inthisfield,foragreeingtotaketimefrombusyschedulestoprovide thesechaptersinatimelyfashion. DavidMortonWaisman Contents Part I. Plasminogen: Structure and Regulation 1. Human Plasminogen: Structure, Activation, and Function FrancisJ. Castellino and Victoria A. Ploplis 1. Introduction 3 2. StructureofHumanPlasminogen. 3 2. 1. PrimaryProteinStructure. 3 2. 2. GeneOrganization 5 3. ActivationofHumanPlasminogen. 6 3. 1. ActivationbyPhysiologicalActivators 7 3. 1. 1. Urokinase-typePlasminogenActivator. 7 3. 1. 2. Tissue-typePlasminogenActivator. 8 3. 2. ActivationbyBacterial-derivedPlasminogenActivators. 9 3. 2. 1. Streptokinase 9 3. 2. 2. Staphylokinase. 9 4. TargetsforPlasminActivity. 9 5. DysplasminogenemiasandPhenotypicManifestations 10 6. Conclusions 11 References. 11 2. Plasminogen Activators: Structure and Function Vincent Ellis 1. Introduction. 19 2. SerineProteases. 20 3. UrokinasePlasminogenActivator,uPA. 21 3. 1. SerineProteaseDomain 22 3. 2. N-terminalDomains. 24 3. 2. 1. KRModule 24 3. 2. 2. EGModule 24 4. MechanismsRegulatinguPAFunction. 25 4. 1. ZymogenActivation. 25 4. 2. ZymogenActivity. 26 4. 3. ReciprocalZymogenActivation 27 4. 4. uPARStimulationofPlasminogenActivation. 27 4. 4. 1. uPAandtheTemplateMechanism 28 4. 4. 2. PlasminogenandtheTemplateMechanism 29 4. 5. AvianuPA,aSpecialCase? 30 xiii x

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