Objectif Biological redox reactions have been identified as control mechanisms for all aspects of cellular life. Extracellular redox signals contribute to cellular communication, including host-tumour and host-pathogen interactions.Recent evidence suggests that disulfide bonds in extracellular domains of cell surface receptors have the potential to act as redox-operated switches for protein function. However, target proteins of extracellular redox activity are mostly unknown and the impact of specific cell surface redox changes on cellular interactions and signal transduction remains to be studied.We propose to identify and functionally analyze redox-regulated surface proteins involved in cellular communication. We will focus on redox signals involved in the activation of primary T cells and in the growth of transformed T cells. Both processes are stimulated by the thiol-disulfide oxidoreductase thioredoxin-1, which is either secreted by dendritic cells in response to antigen-specific recognition of T cells or by T cells themselves as a result of transformation.The extracellular activities of thioredoxin are known to depend on its redox activity. It is not yet understood how redox changes on the cell surface effect increased sensitivity to particular growth factors and cytokines. In order to identify thioredoxin-regulated proteins on T cells we will apply novel strategies of functional proteomics, including mechanism-based trapping with mutant thioredoxin-1.Thioredoxin-based signals and their disruption will be analyzed in a DC-T cell coculture system. We are also pioneering techniques to track redox changes by flow cytometry and thereby aim at correlating in vivo events with specific redox signals. We expect to obtain fundamental insight into the emerging field of extracellular redox signalling. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural scienceschemical sciencesorganic chemistryorganic reactionsnatural scienceschemical scienceselectrochemistryelectrolysisnatural scienceschemical sciencescatalysisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Mots‑clés T cells dendritic cells immunity redox signaling thioredoxin transformation Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Thème(s) MOBILITY-3.1 - Marie Curie Excellence Grants (EXT) Appel à propositions FP6-2002-MOBILITY-8 Voir d’autres projets de cet appel Régime de financement EXT - Marie Curie actions-Grants for Excellent Teams Coordinateur DEUTSCHES KREBSFORSCHUNGSZENTRUM Contribution de l’UE Aucune donnée Adresse Im Neuenheimer Feld 280 HEIDELBERG Allemagne Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée
