Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7573
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dc.contributor.authorFridrich, Sven-
dc.contributor.authorHahn, Susanne A.-
dc.contributor.authorLinzmaier, Marion-
dc.contributor.authorFelten, Matthias-
dc.contributor.authorZwarg, Jenny-
dc.contributor.authorLennerz, Volker-
dc.contributor.authorTüttenberg, Andrea-
dc.contributor.authorStöcker, Walter-
dc.date.accessioned2022-08-19T08:00:20Z-
dc.date.available2022-08-19T08:00:20Z-
dc.date.issued2016-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7587-
dc.description.abstractGARP (glycoprotein A repetitions predominant) is a cell surface receptor on regulatory T-lymphocytes, platelets, hepatic stellate cells and certain cancer cells. Its described function is the binding and accommodation of latent TGFβ (transforming growth factor), before the activation and release of the mature cytokine. For regulatory T cells it was shown that a knockdown of GARP or a treatment with blocking antibodies dramatically decreases their immune suppressive capacity. This confirms a fundamental role of GARP in the basic function of regulatory T cells. Prerequisites postulated for physiological GARP function include membrane anchorage of GARP, disulfide bridges between the propeptide of TGFβ and GARP and connection of this propeptide to αvβ6 or αvβ8 integrins of target cells during mechanical TGFβ release. Other studies indicate the existence of soluble GARP complexes and a functionality of soluble GARP alone. In order to clarify the underlying molecular mechanism, we expressed and purified recombinant TGFβ and a soluble variant of GARP. Surprisingly, soluble GARP and TGFβ formed stable non-covalent complexes in addition to disulfide-coupled complexes, depending on the redox conditions of the microenvironment. We also show that soluble GARP alone and the two variants of complexes mediate different levels of TGFβ activity. TGFβ activation is enhanced by the non-covalent GARP-TGFβ complex already at low (nanomolar) concentrations, at which GARP alone does not show any effect. This supports the idea of soluble GARP acting as immune modulator in vivo.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizinde
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc570 Biowissenschaftende_DE
dc.subject.ddc570 Life sciencesen_GB
dc.titleHow soluble GARP enhances TGFβ activationen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-7573-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.departmentFB 10 Biologiede
jgu.organisation.number2700-
jgu.organisation.number7970-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titlePLoS onede
jgu.journal.volume11de
jgu.journal.issue4de
jgu.pages.alternativee0153290de
jgu.publisher.year2016-
jgu.publisher.namePLoSde
jgu.publisher.placeLawrence, Kan.de
jgu.publisher.urihttp://dx.doi.org/10.1371/journal.pone.0153290de
jgu.publisher.issn1932-6203de
jgu.organisation.placeMainz-
jgu.subject.ddccode570de
opus.date.modified2019-04-15T07:39:20Z-
opus.organisation.stringFB 04: Medizin: III. Medizinische Klinik und Poliklinikde_DE
opus.organisation.stringFB 04: Medizin: Hautklinikde_DE
opus.organisation.stringFB 10: Biologie: Institut für Zoologiede_DE
opus.identifier.opusid53815-
opus.institute.number0427-
opus.institute.number0431-
opus.institute.number1003-
opus.metadataonlyfalse-
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_EN
opus.affiliatedFridrich, Sven-
opus.affiliatedFelten, Matthias-
opus.affiliatedLennerz, Volker-
opus.affiliatedTüttenberg, Andrea-
opus.affiliatedStöcker, Walter-
jgu.publisher.doi10.1371/journal.pone.0153290de
jgu.organisation.rorhttps://ror.org/023b0x485-
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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