Engelke, Michael

[["dc.bibliographiccitation.firstpage","5354"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","The journal of immunology"],["dc.bibliographiccitation.lastpage","5358"],["dc.bibliographiccitation.volume","191"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Wienands, Jürgen"],["dc.date.accessioned","2017-09-07T11:47:02Z"],["dc.date.available","2017-09-07T11:47:02Z"],["dc.date.issued","2013"],["dc.description.abstract","Ag-mediated B cell stimulation relies on phospholipase C gamma 2 (PLC gamma 2) for Ca2+ mobilization. Enzymatic activity of PLC gamma 2 is triggered upon Src homology 2 domain-mediated binding to the tyrosine-phosphorylated adaptor SLP65. However, SLP65 phosphorylation outlasts the elevation of cytosolic Ca2+ concentration suggesting additional levels of PLC gamma 2 regulation. We show in this article that the functionality of the PLC gamma 2/SLP65 complex is controlled by the weakly characterized C2 domain of PLC gamma 2. Usually C2 domains bind membrane lipids, but that of PLC gamma 2 docks in a Ca2+-regulated manner to a distinct phosphotyrosine of SLP65. Hence, early Ca2+ fluxing provides feed-forward signal amplification by promoting anchoring of the PLC gamma 2 C2 domain to phospho-SLP65. As the cellular Ca2+ resources become exhausted, the concomitant decline of Ca2+ dampens the C2-phosphotyrosine interaction so that PLC gamma 2 activation terminates despite sustained SLP65 phosphorylation."],["dc.identifier.doi","10.4049/jimmunol.1301326"],["dc.identifier.gro","3142245"],["dc.identifier.isi","000327180600005"],["dc.identifier.pmid","24166973"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6143"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft [SFB 860, B5]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.eissn","1550-6606"],["dc.relation.issn","0022-1767"],["dc.title","Cutting Edge: Feed-Forward Activation of Phospholipase C gamma 2 via C2 Domain-Mediated Binding to SLP65"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","905"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Immunity"],["dc.bibliographiccitation.lastpage","918"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Schnyder, Tim"],["dc.contributor.author","Castello, Angelo"],["dc.contributor.author","Feest, Christoph"],["dc.contributor.author","Harwood, Naomi E."],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Bruckbauer, Andreas"],["dc.contributor.author","Batista, Facundo D."],["dc.date.accessioned","2018-11-07T08:54:58Z"],["dc.date.available","2018-11-07T08:54:58Z"],["dc.date.issued","2011"],["dc.description.abstract","The B cell receptor (BCR) mediates B cell antigen gathering and acquisition for presentation to T cells. Although the amount of antigen presentation to T cells determines the extent of B cell activation, the molecular mechanisms underlying antigen gathering remain unexplored. Here, through a combination of high-resolution imaging, genetics and quantitative mass spectrometry, we demonstrate that adaptors Grb2 and Dok-3, and ubiquitin ligase Cbl in signaling BCR microclusters mediate association with the microtubule motor dynein. Furthermore, we visualize the localization and movement of these microclusters on the underlying microtubule network. Importantly, disruption of this network or diminished dynein recruitment in Grb2-, Dok-3-, or Cbl-deficient B cells, does not influence microcluster formation or actin-dependent spreading, but abrogates directed movement of microclusters and antigen accumulation. Thus we identify a surprising but pivotal role for dynein and the microtubule network alongside Grb2, Dok-3, and Cbl in antigen gathering during B cell activation."],["dc.description.sponsorship","Cancer Research UK"],["dc.identifier.doi","10.1016/j.immuni.2011.06.001"],["dc.identifier.isi","000292349700011"],["dc.identifier.pmid","21703542"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22795"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","1074-7613"],["dc.title","B Cell Receptor-Mediated Antigen Gathering Requires Ubiquitin Ligase Cbl and Adaptors Grb2 and Dok-3 to Recruit Dynein to the Signaling Microcluster"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1550"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","1562"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Wienands, Juergen"],["dc.date.accessioned","2018-11-07T08:55:23Z"],["dc.date.available","2018-11-07T08:55:23Z"],["dc.date.issued","2011"],["dc.description.abstract","Spleen tyrosine kinase Syk provides critical transducer functions for a number of immune cell receptors and has been implicated in the generation of several forms of leukemias. Catalytic activity and the ability of Syk to interact with other signaling elements depend on the phosphorylation status of Syk. We have now identified and quantified the full spectrum of phosphoacceptor sites in human Syk as well as the interactome of Syk in resting and activated B cells by high-resolution mass spectrometry. While the majority of inducible phosphorylations occurred on tyrosine residues, one of the most frequently detected phosphosites encompassed serine 297 located within the linker insert distinguishing the long and short isoforms of Syk. Full-length Syk can associate with more than 25 distinct ligands including the 14-3-3 gamma adaptor protein, which binds directly to phosphoserine 297. The latter complex attenuates inducible plasma membrane recruitment of Syk, thereby limiting antigen receptor-proximal signaling pathways. Collectively, the established ligand library provides a basis to understand the complexity of the Syk signaling network."],["dc.identifier.doi","10.1002/eji.201041326"],["dc.identifier.isi","000291559700007"],["dc.identifier.pmid","21469132"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22888"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0014-2980"],["dc.title","Complex phosphorylation dynamics control the composition of the Syk interactome 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","966"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nature Immunology"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Castello, Angelo"],["dc.contributor.author","Gaya, Mauro"],["dc.contributor.author","Tucholski, Johannes"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Lu, Kun-Hui"],["dc.contributor.author","Tafuri, Anna"],["dc.contributor.author","Pawson, Tony"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Batista, Facundo D."],["dc.date.accessioned","2018-11-07T09:20:55Z"],["dc.date.available","2018-11-07T09:20:55Z"],["dc.date.issued","2013"],["dc.description.abstract","The adaptor Nck links receptor signaling to cytoskeleton regulation. Here we found that Nck also controlled the phosphatidylinositol-3-OH kinase (PI(3)K)-kinase Akt pathway by recruiting the adaptor BCAP after activation of B cells. Nck bound directly to the B cell antigen receptor (BCR) via the non-immunoreceptor tyrosine-based activation motif (ITAM) phosphorylated tyrosine residue at position 204 in the tail of the immunoglobulin-a component. Genetic ablation of Nck resulted in defective BCR signaling, which led to hampered survival and proliferation of B cells in vivo. Indeed, antibody responses in Nck-deficient mice were also considerably impaired. Thus, we demonstrate a previously unknown adaptor function for Nck in recruiting BCAP to sites of BCR signaling and thereby modulating the PI(3) K-Akt pathway in B cells."],["dc.description.sponsorship","Cancer Research UK; Royal Society"],["dc.identifier.doi","10.1038/ni.2685"],["dc.identifier.isi","000323377700014"],["dc.identifier.pmid","23913047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28988"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1529-2908"],["dc.title","Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway 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","3889"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Blood"],["dc.bibliographiccitation.lastpage","3899"],["dc.bibliographiccitation.volume","121"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Oellerich, Mark F."],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Muench, Silvia"],["dc.contributor.author","Mohr, Sebastian"],["dc.contributor.author","Nimz, Marika"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Corso, Jasmin"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Berg, Tobias"],["dc.contributor.author","Rieger, Michael A."],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Bug, Gesine"],["dc.contributor.author","Brandts, Christian"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Serve, Hubert"],["dc.date.accessioned","2018-11-07T09:24:43Z"],["dc.date.available","2018-11-07T09:24:43Z"],["dc.date.issued","2013"],["dc.description.abstract","Spleen tyrosine kinase (Syk) induces cell survival and proliferation in a high proportion of acute myeloid leukemia (AML) blasts, but the underlying molecular events of Syk signaling have not been investigated. Proteomic techniques have allowed us to identify the multiprotein complex that is nucleated by constitutively active Syk in AML cells. This complex differs from the B-lymphoid Syk interactome with respect to several proteins, especially the integrin receptor Mac-1, the Fc-gamma receptor I (Fc gamma RI), and the transcription factors STAT3 and STAT5. We show in several AML cell line models that tonic signals derived from the Fc-gamma chain lead to Syk-dependent activation of STAT3 and STAT5, which in turn induces cell survival and proliferation. Moreover, stimulation of Mac-1 or Fc gamma RI intensifies the constitutive Syk-mediated STAT3/5 activation in AML cells, a scenario likely to take place in the bone marrow niche. In accordance with these findings, we observed that beta(2) integrins, including Mac-1, trigger proliferation of AML cells in an AML cell/stroma coculture model. Taken together, we identified an oncogenic integrin/Syk/STAT3/5 signaling axis that might serve as a therapeutic target of AML in the future."],["dc.identifier.doi","10.1182/blood-2012-09-457887"],["dc.identifier.isi","000321870900019"],["dc.identifier.pmid","23509157"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29892"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Hematology"],["dc.relation.issn","0006-4971"],["dc.title","beta(2) integrin-derived signals induce cell survival and proliferation of AML blasts by activating a Syk/STAT signaling axis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","893"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Cellular Signalling"],["dc.bibliographiccitation.lastpage","900"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Heine, Ines"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Engelke, Michael"],["dc.date.accessioned","2018-11-07T08:56:49Z"],["dc.date.available","2018-11-07T08:56:49Z"],["dc.date.issued","2011"],["dc.description.abstract","B cells require signals transduced by the B cell antigen receptor (BCR) to provide humoral adaptive immunity. These signals are modulated by co-receptors like the Fc gamma receptor IIb (Fc gamma RIIb) that prevents activation of B cells after co-ligation with the BCR. Positive and negative effectors need to be precisely organized into signaling complexes, which requires adapter proteins like the growth factor receptor-bound protein 2 (Grb2). Here, we address the question how Grb2-mediated signal integration is affected by Fc gamma RIIb. Our data reveal that concomitant engagement of BCR and Fc gamma RIIb leads to markedly increased Grb2-mediated formation of ternary protein complexes comprising downstream of kinase-3 (Dok-3), Grb2, and the SH2 domain-containing inositol phosphatase (SHIP). Consistently, we found Grb2 to be required for full Fc gamma RIIb-mediated negative regulation. To investigate how Fc gamma RIIb influences the entire Grb2 interactions, we utilized quantitative mass spectrometry to make a differential interactome analysis. This approach revealed a shift of Grb2 interactions towards negative regulators like Dok-3. SHIP and SHP-2 and reduced binding to other proteins like CD19. Hence, we provide evidence that Grb2-mediated signal integration is a dynamic process that is important for the crosstalk between the BCR and its co-receptor Fc gamma RIIb. (C) 2011 Elsevier Inc. All rights reserved."],["dc.description.sponsorship","DFG research group [FOR 521]"],["dc.identifier.doi","10.1016/j.cellsig.2011.01.015"],["dc.identifier.isi","000288977400017"],["dc.identifier.pmid","21262349"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23243"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0898-6568"],["dc.title","Fc gamma receptor IIb modulates the molecular Grb2 interaction network in activated 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","2303"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","2313"],["dc.bibliographiccitation.volume","288"],["dc.contributor.author","Loesing, Marion"],["dc.contributor.author","Goldbeck, Ingo"],["dc.contributor.author","Manno, Birgit"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Schnyder, Tim"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Stork, Bjoern"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Batista, Facundo D."],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Engelke, Michael"],["dc.date.accessioned","2018-11-07T09:29:02Z"],["dc.date.available","2018-11-07T09:29:02Z"],["dc.date.issued","2013"],["dc.description.abstract","Recruitment of the growth factor receptor-bound protein 2 (Grb2) by the plasma membrane-associated adapter protein downstream of kinase 3 (Dok-3) attenuates signals transduced by the B cell antigen receptor (BCR). Here we describe molecular details of Dok-3/Grb2 signal integration and function, showing that the Lyn-dependent activation of the BCR transducer kinase Syk is attenuated by Dok-3/Grb2 in a site-specific manner. This process is associated with the SH3 domain-dependent translocation of Dok-3/ Grb2 complexes into BCR microsignalosomes and augmented phosphorylation of the inhibitory Lyn target SH2 domain-containing inositol 5' phosphatase. Hence, our findings imply that Dok-3/ Grb2 modulates the balance between activatory and inhibitory Lyn functions with the aim to adjust BCR signaling efficiency."],["dc.identifier.doi","10.1074/jbc.M112.406546"],["dc.identifier.isi","000314211500020"],["dc.identifier.pmid","23223229"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30925"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","The Dok-3/Grb2 Protein Signal Module Attenuates Lyn Kinase-dependent Activation of Syk Kinase in B Cell Antigen Receptor Microclusters"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5688"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","5693"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Corso, Jasmin"],["dc.contributor.author","Pan, Kuan-Ting"],["dc.contributor.author","Walter, Roland"],["dc.contributor.author","Doebele, Carmen"],["dc.contributor.author","Mohr, Sebastian"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Slabicki, Mikolaj"],["dc.contributor.author","Huellein, Jennifer"],["dc.contributor.author","Comoglio, Federico"],["dc.contributor.author","Rieger, Michael A."],["dc.contributor.author","Zenz, Thorsten"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Oellerich, Thomas"],["dc.date.accessioned","2018-11-07T10:14:14Z"],["dc.date.available","2018-11-07T10:14:14Z"],["dc.date.issued","2016"],["dc.description.abstract","Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets. We identified and quantified similar to 16,000 phospho-sites in BL cells. Among these sites, 909 were related to tonic BCR signaling, whereas 984 phospho-sites were regulated upon BCR engagement. The majority of the identified BCR signaling effectors have not been described in the context of B cells or lymphomas yet. Most of these newly identified BCR effectors are predicted to be involved in the regulation of kinases, transcription, and cytoskeleton dynamics. Although tonic and activated BCR signaling shared a considerable number of effector proteins, we identified distinct phosphorylation events in tonic BCR signaling. We investigated the functional relevance of some newly identified BCR effectors and show that ACTN4 and ARFGEF2, which have been described as regulators of membrane-trafficking and cytoskeleton-related processes, respectively, are crucial for BL cell survival. Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments."],["dc.identifier.doi","10.1073/pnas.1601053113"],["dc.identifier.isi","000375977600058"],["dc.identifier.pmid","27155012"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40583"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.volume","190"],["dc.contributor.author","Castello, Angelo"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Tucholski, Johannes"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Tafuri, Anna"],["dc.contributor.author","Pawson, Tony"],["dc.contributor.author","Batista, Facundo D."],["dc.date.accessioned","2018-11-07T09:24:51Z"],["dc.date.available","2018-11-07T09:24:51Z"],["dc.date.issued","2013"],["dc.identifier.isi","000322987100154"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29928"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Immunologists"],["dc.publisher.place","Bethesda"],["dc.relation.conference","100th Annual Meeting of the American-Association-of-Immunologists"],["dc.relation.eventlocation","Honolulu, HI"],["dc.title","Nck proteins are recruited directly to the BCR and regulate PI3K signaling thereby shaping B cell immune responses"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["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"]]