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Mechanism of plasmin generation by S100A10

2017-06Journal article Restricted access
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dc.contributor.authorMiller, Victoria A.
dc.contributor.authorMadureira, Patricia
dc.contributor.authorKamaludin, Ain Adilliah
dc.contributor.authorKomar, Jeffrey
dc.contributor.authorSharma, Vandna
dc.contributor.authorSahni, Girish
dc.contributor.authorThewell, Craig
dc.contributor.authorLongstaff, Colin
dc.contributor.authorWaisman, David M.
dc.date.accessioned2019-11-20T15:07:34Z
dc.date.available2019-11-20T15:07:34Z
dc.date.issued2017-06
dc.description.abstractPlasminogen (Pg) is cleaved to form plasmin by the action of specific plasminogen activators such as the tissue plasminogen activator (tPA). Although the interaction of tPA and Pg with the surface of the fibrin clot has been well characterised, their interaction with cell surface Pg receptors is poorly understood. S100A10 is a cell surface Pg receptor that plays a key role in cellular plasmin generation. In the present report, we have utilised domain-switched/deleted variants of tPA, truncated plasminogen variants and S100A10 site-directed mutant proteins to define the regions responsible for S100A10-dependent plasmin generation. In contrast to the established role of the finger domain of tPA in fibrin-stimulated plasmin generation, we show that the kringle-2 domain of tPA plays a key role in S100A10-dependent plasmin generation. The kringle-1 domain of plasminogen, indispensable for fibrin-binding, is also critical for S100A10-dependent plasmin generation. S100A10 retains activity after substitution or deletion of the carboxyl-terminal lysine suggesting that internal lysine residues contribute to its plasmin generating activity. These studies define a new paradigm for plasminogen activation by the plasminogen receptor, S100A10.
dc.description.sponsorshipHeart and Stroke Foundation of Canada [G-14-0005821]
dc.description.sponsorshipFCT Investigator from Fundacao para a Ciencia e a Tecnologia, Portugal [IF/00614/2014]
dc.description.sponsorshipnational Portuguese funding through FCT Fundacao para a Ciencia e a Tecnologia [UID/BIM/04773/2013 CBMR]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1160/TH16-12-0936
dc.identifier.issn0340-6245
dc.identifier.urihttp://hdl.handle.net/10400.1/13105
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSchattauer Gmbh-Verlag Medizin Naturwissenschaften
dc.subjectAnnexin li tetramer
dc.subjectCellular-binding sites
dc.subjectStreptococcus-pneumoniae
dc.subjectA2 heterotetramer
dc.subjectCrystal-structure
dc.subjectAlpha-enolase
dc.subjectP11 subunit
dc.subjectActivator
dc.subjectFibrinolysis
dc.subjectSurface
dc.titleMechanism of plasmin generation by S100A10
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1071
oaire.citation.issue6
oaire.citation.startPage1058
oaire.citation.titleThrombosis and Haemostasis
oaire.citation.volume117
person.familyNameMadureira
person.givenNamePatricia
person.identifier.ciencia-id6612-9A86-6929
person.identifier.orcid0000-0002-4856-3908
person.identifier.scopus-author-id10340140500
rcaap.rightsrestrictedAccess
rcaap.typearticle
relation.isAuthorOfPublicationa40de6a3-d52d-45dd-8620-cb94a22ebc8f
relation.isAuthorOfPublication.latestForDiscoverya40de6a3-d52d-45dd-8620-cb94a22ebc8f

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