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
Les informations fournies dans la section « Synopsis » peuvent faire référence à une autre édition de ce titre.
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Taschenbuch. Etat : Neu. This item is printed on demand - it takes 3-4 days longer - Neuware -TheobservationthatabloodclotspontaneouslydissolveswasfirstdescribedbyDenys in1889. Subsequently,thebloodclottingsystemwasshowntobeinvolvedintumor growth. Forexample,asearlyas1925,Fisherreportedthataviantissueexplantstrans formedtomalignancybyvirusesgeneratedhighlevelsoffibrinolyticactivityu ndercon ditionsinwhichculturesofnormalcellsdidnot. In1958,theconceptthatan equilibriumexistedbetweenthetendencyofbloodtoclotandtoremainfluidwaspro posedbyAstrup. Atthattime,itwasbelievedthatthishemostaticbalancewasexplained bytheabilityofpolymerizingfibrintoorchestrateitsownclearancebystimulatingfib rinolyticactivity. Sincethesepioneeringstudies,considerableinformationhasaccumu latedthathasdefinedthecomponentsofthecoagulationandfibrinolyticsystemsand howtheyareinvolvedinphysiologicalandpathophysiologicalprocesses. Plasminogen: Structure, activation, and regulationfocusesonthebasicprinciplesandrecentdevelop mentsintheplasminogen/plasminresearchfieldandhowtheseresultsprovideacon ceptualframeworkforanunderstandingofthephysiologicalroleofplasminogenin healthanddisease. Theenzymaticcascadetriggeredbyactivationofplasminogenhasbeenimpl icated inavarietyofnormalandpathologicaleventssuchasfibrinolysis,woundhealing,tis sueremodeling,embryogenesis,angiogenesis,andtheinvasionandmetastasisoftumor cells. Thisimpressivelistofphysiologicalfunctionsforplasminogenreinforcesthewide diversityofrolesthatplasminogenplaysinvariousphysiologicalpro cesses. Productive plasmingenerationrequirestheassemblyofbothplasminogenactivatorsandplasmino genonasolidsupportsuchasthefibrinpolymerorthecellsurface. Theregulationof plasminproductioninvolvesacomplexinterplaybetweentheseplasminogenactivat ors, plasminogenactivatorinhibitors,andplasmininhibitors. Clearly,theexplosivegrowth inthisresearchfieldandthemanyexcitingdiscoveriessuggeststhattheresearchefforts inthenextdecadewillrevealthemechanismsbywhichthecomponentsoftheplas minogensysteminteractandregulatebothplasminactivationandfunctionatac ellular level. Plasminogen: Structure, activation, and regulationisdividedintotwosections. Thefirstsectiondealswiththestructureandregulationofplasminogen. Thechapters inthissectionrangefromdiscussionsofthestructureofplasminogenandtheregulat ion oftheplasminogengenetodiscussionsofthestructureandregulationofplasminogen activatorsandplasminogenactivatorinhibitors. Alsoexaminedistherelativelynewdata concerningthegenerationofanti-angiogenicmoleculesfromplasminogen. Thesecond sectiondealswiththephysiologicalandpathophysiologicalrolesofplasmi nogenaswell astheconsequencesofplasminogengeneknockout. Discussionsinthissectioninclude examinationoftheroleofplasminogeninhematopoieticmalignancies,tumorcell progression,angiogenesis,mammaryglandinvolution,woundhealing,andbone readsorption. xi xii Preface Inclosing,Iwouldliketothankmyadministrativeassistant,Ms. ViSommerfeld,for herinvaluableassistanceandtimelesseffortswiththeorganizationandeditingofthebook. Lastly,Iwouldliketoacknowledgetheeffortsoftheauthorsoftheindividualc hapters, 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. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . N° de réf. du vendeur 9781461349495
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Taschenbuch. Etat : Neu. This item is printed on demand - Print on Demand Titel. Neuware -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-typeSpringer Verlag GmbH, Tiergartenstr. 17, 69121 Heidelberg 320 pp. Englisch. N° de réf. du vendeur 9781461349495
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