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 xiv Contents 5. TissuePlasminogenActivator,tPA. 30 5. 1. SerineProteaseDomain 31 5. 2. N-terminalDomains ,. 33 5. 2. 1. KRModules ,. ,. ,. 33 5. 2. 2. F1-EGSupermodule 33 6.
Waisman
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I. Plasminogen: Structure and Regulation.- 1. Human Plasminogen: Structure, Activation, and Function.- 2. Plasminogen Activators: Structure and Function.- 3. Plasminogen Activators Inhibitors.- 4. Regulation of Plasminogen Gene Expression.- 5. Plasminogen Receptors.- 6. The Role of Lys-Plasminogen in Cell-Mediated Plasmin Production.- 7. Plasmin Reductase.- 8. Mechanism of Angiostatin Formation from Plasminogen.- II. Physiological Roles of Plasminogen.- 9. Lessons Learned from the Pig Deficient Mice (Plg—/—).- 10. Plasminogen-Directed Phenotypes in Mice.- 11. Role of the Plasminogen and MMP Systems in Wound Healing.- 12. Matrix Metalloproteinases and the Plasminogen System in Tumor Progression.- 13. Role of Plasminogen Activation in Hematopoietic Malignancies and in Normal Hematopoiesis.- 14. The Role of Plasminogen in Bone Remodeling.- 15. Plasminogen Activators in CNS Physiology and Disease.- 16. Role of the Plasminogen Activator-Plasmin System in Angiogenesis.
