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Plasminogen: Structure, Activation, and Regulation
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ISBN10: 1461349494
ISBN13: 9781461349495
Publisher: Springer Nature
Published: Sep 17 2012
Pages: 293
Weight: 1.23
Height: 0.67 Width: 7.00 Depth: 10.00
Language: English
ISBN13: 9781461349495
Publisher: Springer Nature
Published: Sep 17 2012
Pages: 293
Weight: 1.23
Height: 0.67 Width: 7.00 Depth: 10.00
Language: English
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...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
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