Engelke, Michael

[["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","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","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.firstpage","44"],["dc.bibliographiccitation.journal","Immunology Letters"],["dc.bibliographiccitation.lastpage","52"],["dc.bibliographiccitation.volume","243"],["dc.contributor.author","Gayer, Fabian A."],["dc.contributor.author","Reichardt, Sybille D."],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Reichardt, Holger M."],["dc.date.accessioned","2022-04-01T10:02:27Z"],["dc.date.available","2022-04-01T10:02:27Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1016/j.imlet.2022.02.003"],["dc.identifier.pii","S0165247822000220"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105914"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.issn","0165-2478"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Characterization of testicular macrophage subpopulations in mice"],["dc.type","journal_article"],["dc.type.internalPublication","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"]]

[["dc.bibliographiccitation.firstpage","598"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Blood"],["dc.bibliographiccitation.lastpage","608"],["dc.bibliographiccitation.volume","129"],["dc.contributor.author","Walter, Roland"],["dc.contributor.author","Pan, Kuan-Ting"],["dc.contributor.author","Doebele, Carmen"],["dc.contributor.author","Comoglio, Federico"],["dc.contributor.author","Tomska, Katarzyna"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Young, Ryan M."],["dc.contributor.author","Jacobs, Laura"],["dc.contributor.author","Keller, Ulrich"],["dc.contributor.author","Boenig, Halvard"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Rosenwald, Andreas"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Staudt, Louis M."],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Zenz, Thorsten"],["dc.contributor.author","Oellerich, Thomas"],["dc.date.accessioned","2018-11-07T10:27:35Z"],["dc.date.available","2018-11-07T10:27:35Z"],["dc.date.issued","2017"],["dc.description.abstract","Burkitt lymphoma (BL) is an aggressive B-cell neoplasmthat is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Because of their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Targeted therapies for BL are therefore needed. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival. We found that inhibitors of heat shock protein 90 (HSP90) induced apoptosis in BL cells in vitro at concentrations that did not affect normal B cells. By global proteomic and phosphoproteomic profiling, we show that, in BL, HSP90 inhibition compromises the activity of the pivotal B-cell antigen receptor (BCR)-proximal effector spleen tyrosine kinase (SYK), whichwe identified as an HSP90 client protein. Consistently, expression of constitutively active TEL-SYK counteracted the apoptotic effect of HSP90 inhibition. Together, our results demonstrate that HSP90 inhibition impairs BL cell survival by interfering with tonic BCR signaling, thus providing a molecular rationale for the use of HSP90 inhibitors in the treatment of BL."],["dc.identifier.doi","10.1182/blood-2016-06-721423"],["dc.identifier.isi","000397016100012"],["dc.identifier.pmid","28064214"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43263"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Soc Hematology"],["dc.relation.issn","1528-0020"],["dc.relation.issn","0006-4971"],["dc.title","HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B-cell receptor signaling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]