Bitte benutzen Sie diese Kennung, um auf die Ressource zu verweisen: http://doi.org/10.25358/openscience-7573
Autoren: Fridrich, Sven
Hahn, Susanne A.
Linzmaier, Marion
Felten, Matthias
Zwarg, Jenny
Lennerz, Volker
Tüttenberg, Andrea
Stöcker, Walter
Titel: How soluble GARP enhances TGFβ activation
Online-Publikationsdatum: 19-Aug-2022
Erscheinungsdatum: 2016
Sprache des Dokuments: Englisch
Zusammenfassung/Abstract: GARP (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.
DDC-Sachgruppe: 570 Biowissenschaften
570 Life sciences
Veröffentlichende Institution: Johannes Gutenberg-Universität Mainz
Organisationseinheit: FB 04 Medizin
FB 10 Biologie
Veröffentlichungsort: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-7573
Version: Published version
Publikationstyp: Zeitschriftenaufsatz
Nutzungsrechte: CC BY
Informationen zu den Nutzungsrechten: https://creativecommons.org/licenses/by/4.0/
Zeitschrift: PLoS one
11
4
Seitenzahl oder Artikelnummer: e0153290
Verlag: PLoS
Verlagsort: Lawrence, Kan.
Erscheinungsdatum: 2016
ISSN: 1932-6203
URL der Originalveröffentlichung: http://dx.doi.org/10.1371/journal.pone.0153290
DOI der Originalveröffentlichung: 10.1371/journal.pone.0153290
Enthalten in den Sammlungen:DFG-OA-Publizieren (2012 - 2017)

Dateien zu dieser Ressource:
  Datei Beschreibung GrößeFormat
Miniaturbild
how_soluble_garp_enhances_tgf-20220817161800649.pdf1.34 MBAdobe PDFÖffnen/Anzeigen