Wienands, Jürgen

[["dc.bibliographiccitation.firstpage","1083"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1099"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","John, Michael"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Goetz, Alexander A."],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Borisch, Angela"],["dc.contributor.author","Boutin, Philippe"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Bremes, Vanessa"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Waetzig, Vicky"],["dc.contributor.author","Herdegen, Thomas"],["dc.contributor.author","Teismann, Peter"],["dc.contributor.author","Greig, Iain"],["dc.contributor.author","Mueller, Michael"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Mildner, Alexander"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Rotshenker, Shlomo"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T09:56:53Z"],["dc.date.available","2018-11-07T09:56:53Z"],["dc.date.issued","2015"],["dc.description.abstract","The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK inhibition cannot account for the entire activity spectrum. Effects on TLR-induced proinflammatory cytokine expression in microglia involve AG126 hydrolysis and conversion of its dinitrile side chain to malononitrile (MN). Notably, while liberated MN can subsequently mediate critical AG126 features, full protection in EAE still requires delivery of intact AG126. Its anti-inflammatory potential and especially interference with TLR signaling thus rely on a dual mechanism encompassing BTK and a novel MN-sensitive target. Both principles bear great potential for the therapeutic management of disturbed innate and adaptive immune functions. GLIA 2015;63:1083-1099"],["dc.identifier.doi","10.1002/glia.22803"],["dc.identifier.isi","000353244400011"],["dc.identifier.pmid","25731696"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37056"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1098-1136"],["dc.relation.issn","0894-1491"],["dc.title","Tyrphostin AG126 Exerts Neuroprotection in CNS Inflammation by a Dual Mechanism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1738"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Molecular & Cellular Proteomics"],["dc.bibliographiccitation.lastpage","1750"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Gronborg, Mads"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Wienands, Juergen"],["dc.date.accessioned","2018-11-07T08:28:22Z"],["dc.date.available","2018-11-07T08:28:22Z"],["dc.date.issued","2009"],["dc.description.abstract","Understanding intracellular signal transduction by cell surface receptors requires information about the precise order of relevant modifications on the early transducer elements. Here we introduce the B cell line DT40 and its genetically engineered variants as a model system to determine and functionally characterize post-translational protein modifications in general. This is accomplished by a customized strategy that combines mass spectrometric analyses of protein modifications with subsequent mutational studies. When applied to the B cell receptor (BCR)proximal effector SLP-65, this approach uncovered a differential and highly dynamic engagement of numerous newly identified phospho-acceptor sites. Some of them serve as kinase substrates in resting cells and undergo rapid dephosphorylation upon BCR ligation. Stimulation-induced phosphorylation of SLP-65 can be early and transient, or early and sustained, or late. Functional elucidation of conspicuous phosphorylation at serine 170 in SLP-65 revealed a BCR-distal checkpoint for some but not all possible B cell responses. Our data show that SLP-65 phosphorylation acts upstream for signal initiation and also downstream during selective processing of the BCR signal. Such a phenomenon defines a receptor-specific signal integrator. Molecular & Cellular Proteomics 8: 1738-1750, 2009."],["dc.description.sponsorship","European Union, HYBLIB"],["dc.identifier.doi","10.1074/mcp.M800567-MCP200"],["dc.identifier.isi","000267960300023"],["dc.identifier.pmid","19372136"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6257"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16410"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","1535-9476"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","SLP-65 Phosphorylation Dynamics Reveals a Functional Basis for Signal Integration by Receptor-proximal Adaptor Proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","135"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Immunological Reviews"],["dc.bibliographiccitation.lastpage","149"],["dc.bibliographiccitation.volume","232"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Wienands, Jürgen"],["dc.date.accessioned","2011-04-21T09:31:50Z"],["dc.date.accessioned","2021-10-27T13:22:42Z"],["dc.date.available","2011-04-21T09:31:50Z"],["dc.date.available","2021-10-27T13:22:42Z"],["dc.date.issued","2009"],["dc.description.abstract","The growth factor receptor-bound protein 2 (Grb2) is a ubiquitously expressed and evolutionary conserved adapter protein possessing a plethora of described interaction partners for the regulation of signal transduction. In B lymphocytes, the Grb2-mediated scaffolding function controls the assembly and subcellular targeting of activating as well as inhibitory signalosomes in response to ligation of the antigen receptor. Also, integration of simultaneous signals from B-cell coreceptors that amplify or attenuate antigen receptor signal output relies on Grb2. Hence, Grb2 is an essential signal integrator. The key question remains, however, of how pathway specificity can be maintained during signal homeostasis critically required for the balance between immune cell activation and tolerance induction. Here, we summarize the molecular network of Grb2 in B cells and introduce a proteomic approach to elucidate the interactome of Grb2 in vivo."],["dc.identifier.doi","10.1111/j.1600-065X.2009.00845.x"],["dc.identifier.isi","000271057600011"],["dc.identifier.pmid","19909361"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92119"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1600-065X"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","B-Lymphocytes"],["dc.subject.mesh","GRB2 Adaptor Protein"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Immune Tolerance"],["dc.subject.mesh","Lymphocyte Activation"],["dc.subject.mesh","Protein Interaction Domains and Motifs"],["dc.subject.mesh","Protein Multimerization"],["dc.subject.mesh","Proteomics"],["dc.subject.mesh","Receptor Cross-Talk"],["dc.subject.mesh","Receptors, Antigen, B-Cell"],["dc.subject.mesh","Signal Transduction"],["dc.title","The B-lymphoid Grb2 interaction code."],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1140"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.lastpage","1149"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Stork, Bjoern"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Goldbeck, Ingo"],["dc.contributor.author","Alers, Sebastian"],["dc.contributor.author","Kaehne, Thilo"],["dc.contributor.author","Naumann, Michael"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Wienands, Juergen"],["dc.date.accessioned","2018-11-07T11:04:54Z"],["dc.date.available","2018-11-07T11:04:54Z"],["dc.date.issued","2007"],["dc.description.abstract","Spatial and temporal modulation of intracellular Ca2+ fluxes controls the cellular response of B lymphocytes to antigen stimulation. Herein, we identify the hematopoietic adaptor protein Dok-3 (downstream of kinase-3) as a key component of negative feedback regulation in Ca2+ signaling from the B-cell antigen receptor. Dok-3 localizes at the inner leaflet of the plasma membrane and is a major substrate for activated Src family kinase Lyn. Phosphorylated Dok-3 inhibits antigen receptor-induced Ca2+ elevation by recruiting cytosolic Grb2, which acts at this location as a negative regulator of Bruton's tyrosine kinase. This leads to diminished activation of phospholipase C-gamma 2 and reduced production of soluble inositol trisphosphate. Hence, the Dok-3/ Grb2 module is a membrane-associated signaling organizer, which orchestrates the interaction efficiency of Ca2+-mobilizing enzymes."],["dc.identifier.doi","10.1038/sj.emboj.7601557"],["dc.identifier.isi","000244387500021"],["dc.identifier.pmid","17290227"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51949"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0261-4189"],["dc.title","Subcellular localization of Grb2 by the adaptor protein Dok-3 restricts the intensity of Ca2+ signaling in B cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3620"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.lastpage","3634"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Bremes, Vanessa"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Schnyder, Tim"],["dc.contributor.author","Batista, Facundo D."],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Wienands, Juergen"],["dc.date.accessioned","2018-11-07T08:53:03Z"],["dc.date.available","2018-11-07T08:53:03Z"],["dc.date.issued","2011"],["dc.description.abstract","Spleen tyrosine kinase Syk and its substrate SLP65 (also called BLNK) are proximal signal transducer elements of the B-cell antigen receptor (BCR). Yet, our understanding of signal initiation and processing is limited owing to the incomplete list of SLP65 interaction partners and our ignorance of their association kinetics. We have now determined and quantified the in vivo interactomes of SLP65 in resting and stimulated B cells by mass spectrometry. SLP65 orchestrated a complex signal network of about 30 proteins that was predominantly based on dynamic interactions. However, a stimulation-independent and constant association of SLP65 with the Cbl-interacting protein of 85 kDa (CIN85) was requisite for SLP65 phosphorylation and its inducible plasma membrane translocation. In the absence of a steady SLP65/CIN85 complex, BCR-induced Ca(2+) and NF-kappa B responses were abrogated. Finally, live cell imaging and co-immunoprecipitation experiments further confirmed that both SLP65 and CIN85 are key components of the BCR-associated primary transducer module required for the onset and progression phases of BCR signal transduction. The EMBO Journal (2011) 30, 3620-3634. doi:10.1038/emboj.2011.251; Published online 5 August 2011"],["dc.identifier.doi","10.1038/emboj.2011.251"],["dc.identifier.isi","000294460000015"],["dc.identifier.pmid","21822214"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7839"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22317"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0261-4189"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2520"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","2530"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Manno, Birgit"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Schnyder, Tim"],["dc.contributor.author","Corso, Jasmin"],["dc.contributor.author","Loesing, Marion"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Batista, Facundo D."],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Wienands, Juergen"],["dc.date.accessioned","2018-11-07T10:05:58Z"],["dc.date.available","2018-11-07T10:05:58Z"],["dc.date.issued","2016"],["dc.description.abstract","The SH2 domain-containing inositol 5'-phosphatase (SHIP) plays a key role in preventing autoimmune phenomena by limiting antigen-mediated B cell activation. SHIP function is thought to require the dual engagement of the BCR and negative regulatory coreceptors as only the latter appear capable of recruiting SHIP from the cytosol to the plasma membrane by the virtue of phosphorylated immunoreceptor tyrosine-based inhibitory motifs. Here, we demonstrate a coreceptor-independent membrane recruitment and function of SHIP in B cells. In the absence of coreceptor ligation, SHIP translocates to sites of BCR activation through a concerted action of the protein adaptor unit Dok-3/Grb2 and phosphorylated BCR signaling components. Our data reveal auto-inhibitory SHIP activation by the activated BCR and suggest an unexpected negative-regulatory capacity of immunoreceptor tyrosine-based activation motifs in Ig alpha and Ig beta."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [TRR130]; University Medicine Gottingen"],["dc.identifier.doi","10.1002/eji.201646431"],["dc.identifier.isi","000392940100006"],["dc.identifier.pmid","27550373"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39006"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1521-4141"],["dc.relation.issn","0014-2980"],["dc.title","The Dok-3/Grb2 adaptor module promotes inducible association of the lipid phosphatase SHIP with the BCR in a coreceptor-independent manner"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]