Plasminogen: Structure, Activation, and Regulation

TheobservationthatabloodclotspontaneouslydissolveswasfirstdescribedbyDenys in1889. Subsequently,thebloodclottingsystemwasshowntobeinvolvedintumor growth. Forexample,asearlyas1925,Fisherreportedthataviantissueexplantstrans formedtomalignancybyvirusesgeneratedhighlevelsoffibrinolyticactivityundercon ditionsinwhichculturesofnormalcellsdidnot. In1958,theconceptthatan equilibriumexistedbetweenthetendencyofbloodtoclotandtoremainfluidwaspro posedbyAstrup. Atthattime,itwasbelievedthatthishemostaticbalancewasexplained bytheabilityofpolymerizingfibrintoorchestrateitsownclearancebystimulatingfib rinolyticactivity. Sincethesepioneeringstudies,considerableinformationhasaccumu latedthathasdefinedthecomponentsofthecoagulationandfibrinolyticsystemsand howtheyareinvolvedinphysiologicalandpathophysiologicalprocesses. Plasminogen: Structure, activation, and regulationfocusesonthebasicprinciplesandrecentdevelop mentsintheplasminogen/plasminresearchfieldandhowtheseresultsprovideacon ceptualframeworkforanunderstandingofthephysiologicalroleofplasminogenin healthanddisease. Theenzymaticcascadetriggeredbyactivationofplasminogenhasbeenimplicated inavarietyofnormalandpathologicaleventssuchasfibrinolysis,woundhealing,tis sueremodeling,embryogenesis,angiogenesis,andtheinvasionandmetastasisoftumor cells. Thisimpressivelistofphysiologicalfunctionsforplasminogenreinforcesthewide diversityofrolesthatplasminogenplaysinvariousphysiologicalprocesses. Productive plasmingenerationrequirestheassemblyofbothplasminogenactivatorsandplasmino genonasolidsupportsuchasthefibrinpolymerorthecellsurface. Theregulationof plasminproductioninvolvesacomplexinterplaybetweentheseplasminogenactivators, plasminogenactivatorinhibitors,andplasmininhibitors. Clearly,theexplosivegrowth 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. . .

List of contents

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.

Product details

• Assisted by: Davi M Waisman (Editor), David M Waisman (Editor), David M. Waisman (Editor)
• Publisher: Springer, Berlin
• Languages: English
• Product format: Paperback / Softback
• Released: 16.10.2013
• EAN: 9781461349495
• ISBN: 978-1-4613-4949-5
• No. of pages: 293
• Dimensions: 178 mm x 17 mm x 254 mm
• Weight: 605 g
• Illustrations: XXI, 293 p.
• Subjects: Natural sciences, medicine, IT, technology > Biology > Biochemistry, biophysics; C, HUMAN PHYSIOLOGY, PHYSIOLOGY, Hematology, biochemistry, Oncology, Biomedical and Life Sciences, Biochemistry, general, Haematology