Engelke, Michael

[["dc.bibliographiccitation.firstpage","1452"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","FEBS Letters"],["dc.bibliographiccitation.lastpage","1458"],["dc.bibliographiccitation.volume","586"],["dc.contributor.author","Junek, Stephan"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Schild, Detlev"],["dc.contributor.author","Wienands, Juergen"],["dc.date.accessioned","2018-11-07T09:10:18Z"],["dc.date.available","2018-11-07T09:10:18Z"],["dc.date.issued","2012"],["dc.description.abstract","Antigen-induced B cell activation requires mobilization of the Ca2+ second messenger. This process is associated with the subcellular relocalization of signal effector proteins of the B cell antigen receptor such as the adaptor protein SLP65. Here we describe a broadly applicable live cell imaging method to simultaneously visualize intracellular Ca2+ flux profiles and the translocation of cytosolic signaling proteins to the plasma membrane in real time. Our approach delineated the kinetic hierarchy of Ca2+ signaling events in B cells and revealed a timely ordered contribution of various organelles to the overall Ca2+ signal. The developed experimental setup provides a useful tool to resolve the spatiotemporal signaling dynamics in various receptor signaling systems. (c) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.febslet.2012.03.057"],["dc.identifier.isi","000304104200011"],["dc.identifier.pmid","22673510"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9753"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26456"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0014-5793"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Spatiotemporal resolution of Ca2+ signaling events by real time imaging of single B cells"],["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","1480"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","1502"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Isernhagen, Antje"],["dc.contributor.author","Malzahn, Doerthe"],["dc.contributor.author","Viktorova, Elena"],["dc.contributor.author","Elsner, Leslie"],["dc.contributor.author","Monecke, Sebastian"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Kilisch, Markus"],["dc.contributor.author","Wermuth, Janne Marieke"],["dc.contributor.author","Walther, Neele"],["dc.contributor.author","Balavarca, Yesilda"],["dc.contributor.author","Stahl-Hennig, Christiane"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Bickeboeller, Heike"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Wulf, Gerald"],["dc.contributor.author","Dressel, Ralf"],["dc.date.accessioned","2018-11-07T09:49:36Z"],["dc.date.available","2018-11-07T09:49:36Z"],["dc.date.issued","2015"],["dc.description.abstract","The MHC class I chain-related molecule A (MICA) is a highly polymorphic ligand for the activating natural killer (NK)-cell receptor NKG2D. A single nucleotide polymorphism causes a valine to methionine exchange at position 129. Presence of a MICA-129Met allele in patients (n=452) undergoing hematopoietic stem cell transplantation (HSCT) increased the chance of overall survival (hazard ratio [HR]=0.77, P=0.0445) and reduced the risk to die due to acute graft-versus-host disease (aGVHD) (odds ratio [OR]=0.57, P=0.0400) although homozygous carriers had an increased risk to experience this complication (OR=1.92, P=0.0371). Overall survival of MICA-129Val/Val genotype carriers was improved when treated with anti-thymocyte globulin (HR=0.54, P=0.0166). Functionally, the MICA-129Met isoform was characterized by stronger NKG2D signaling, triggering more NK-cell cytotoxicity and interferon- release, and faster co-stimulation of CD8(+) T cells. The MICA-129Met variant also induced a faster and stronger down-regulation of NKG2D on NK and CD8(+) T cells than the MICA-129Val isoform. The reduced cell surface expression of NKG2D in response to engagement by MICA-129Met variants appeared to reduce the severity of aGVHD."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.15252/emmm.201505246"],["dc.identifier.isi","000364320100008"],["dc.identifier.pmid","26483398"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12462"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35542"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/127"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C05: Bedeutung von zellulären Immunreaktionen für das kardiale Remodeling und die Therapie der Herzinsuffizienz durch Stammzelltransplantation"],["dc.relation.issn","1757-4684"],["dc.relation.issn","1757-4676"],["dc.relation.workinggroup","RG Dressel"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","43"],["dc.bibliographiccitation.journal","Cell Communication and Signaling"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schrader, Alexandra"],["dc.contributor.author","Meyer, Katharina"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Walther, Neele"],["dc.contributor.author","Hand, Elisabeth"],["dc.contributor.author","Ulrich, Antje"],["dc.contributor.author","Matulewicz, Kamila"],["dc.contributor.author","Lenze, Dido"],["dc.contributor.author","Hummel, Michael"],["dc.contributor.author","Kieser, Arnd"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2018-11-07T09:02:13Z"],["dc.date.available","2018-11-07T09:02:13Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Aggressive Non-Hodgkin lymphomas (NHL) are a group of lymphomas derived from germinal centre B cells which display a heterogeneous pattern of oncogenic pathway activation. We postulate that specific immune response associated signalling, affecting gene transcription networks, may be associated with the activation of different oncogenic pathways in aggressive Non-Hodgkin lymphomas (NHL). Methodology: The B cell receptor (BCR), CD40, B-cell activating factor (BAFF)-receptors and Interleukin (IL) 21 receptor and Toll like receptor 4 (TLR4) were stimulated in human transformed germinal centre B cells by treatment with anti IgM F(ab)(2)-fragments, CD40L, BAFF, IL21 and LPS respectively. The changes in gene expression following the activation of Jak/STAT, NF-kappa B, MAPK, Ca2+ and PI3K signalling triggered by these stimuli was assessed using microarray analysis. The expression of top 100 genes which had a change in gene expression following stimulation was investigated in gene expression profiles of patients with Aggressive non-Hodgkin Lymphoma (NHL). Results: alpha IgM stimulation led to the largest number of changes in gene expression, affecting overall 6596 genes. While CD40L stimulation changed the expression of 1194 genes and IL21 stimulation affected 902 genes, only 283 and 129 genes were modulated by lipopolysaccharide or BAFF receptor stimulation, respectively. Interestingly, genes associated with a Burkitt-like phenotype, such as MYC, BCL6 or LEF1, were affected by alpha IgM. Unique and shared gene expression was delineated. NHL-patients were sorted according to their similarity in the expression of TOP100 affected genes to stimulated transformed germinal centre B cells The alpha IgM gene module discriminated individual DLBCL in a similar manner to CD40L or IL21 gene modules. DLBCLs with low module activation often carry chromosomal MYC aberrations. DLBCLs with high module activation show strong expression of genes involved in cell-cell communication, immune responses or negative feedback loops. Using chemical inhibitors for selected kinases we show that mitogen activated protein kinase-and phosphoinositide 3 kinase-signalling are dominantly involved in regulating genes included in the alpha IgM gene module. Conclusion: We provide an in vitro model system to investigate pathway activation in lymphomas. We defined the extent to which different immune response associated pathways are responsible for differences in gene expression which distinguish individual DLBCL cases. Our results support the view that tonic or constitutively active MAPK/ERK pathways are an important part of oncogenic signalling in NHL. The experimental model can now be applied to study the therapeutic potential of deregulated oncogenic pathways and to develop individual treatment strategies for lymphoma patients."],["dc.identifier.doi","10.1186/1478-811X-10-43"],["dc.identifier.isi","000314937400001"],["dc.identifier.pmid","23253402"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8528"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24629"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1478-811X"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Global gene expression changes of in vitro stimulated human transformed germinal centre B cells as surrogate for oncogenic pathway activation in individual aggressive B cell lymphomas"],["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.artnumber","A73"],["dc.bibliographiccitation.issue","Suppl 1"],["dc.bibliographiccitation.journal","Cell Communication and Signaling"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Engelke, M."],["dc.contributor.author","Li, X."],["dc.contributor.author","Manno, B."],["dc.contributor.author","Neumann, K."],["dc.contributor.author","Wienands, J."],["dc.date.accessioned","2011-04-18T14:05:52Z"],["dc.date.accessioned","2021-10-27T13:22:40Z"],["dc.date.available","2011-04-18T14:05:52Z"],["dc.date.available","2021-10-27T13:22:40Z"],["dc.date.issued","2009"],["dc.identifier.doi","10.1186/1478-811X-7-S1-A73"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6164"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92116"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","B cell antigen receptor-induced plasma membrane recruitment of the SH2 domain-containing inositol phosphatase is mediated by the protein tyrosine kinases Lyn and Syk"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e16370"],["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Justa-Schuch, Daniela"],["dc.contributor.author","Silva-Garcia, Maria"],["dc.contributor.author","Pilla, Esther"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Kilisch, Markus"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Möller, Ulrike"],["dc.contributor.author","Nakamura, Fumihiko"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Geiss-Friedlander, Ruth"],["dc.date.accessioned","2021-06-01T10:48:59Z"],["dc.date.available","2021-06-01T10:48:59Z"],["dc.date.issued","2016"],["dc.description.abstract","The aminopeptidase DPP9 removes dipeptides from N-termini of substrates having a proline or alanine in second position. Although linked to several pathways including cell survival and metabolism, the molecular mechanisms underlying these outcomes are poorly understood. We identified a novel interaction of DPP9 with Filamin A, which recruits DPP9 to Syk, a central kinase in B-cell signalling. Syk signalling can be terminated by degradation, requiring the ubiquitin E3 ligase Cbl. We show that DPP9 cleaves Syk to produce a neo N-terminus with serine in position 1. Pulse-chases combined with mutagenesis studies reveal that Ser1 strongly influences Syk stability. Furthermore, DPP9 silencing reduces Cbl interaction with Syk, suggesting that DPP9 processing is a prerequisite for Syk ubiquitination. Consistently, DPP9 inhibition stabilizes Syk, thereby modulating Syk signalling. Taken together, we demonstrate DPP9 as a negative regulator of Syk and conclude that DPP9 is a novel integral aminopeptidase of the N-end rule pathway."],["dc.description.abstract","Proteins are made up of building blocks called amino acids bonded together to form chain-like molecules. Around twenty different amino acids are used to make proteins, and enzymes called proteases can recognize specific pairs of amino acids in proteins and cut the bonds between them. Dipeptidylpeptidase 9 (or DPP9 for short) is a protease that removes two amino acids from the end of a protein, just as long the second amino acid is one of two specific kinds (namely, an alanine or a proline). The DPP9 protease influences a range of processes in the cell including cell death, signaling and survival. Indeed, mice born with an inactive version of DPP9 die shortly after birth, but it is not known why this happens. Justa-Schuch et al. investigated how the protease DPP9 controls processes inside cells and found an unexpected connection between DPP9 and another protein called Syk. The Syk protein is found in immune cells called B cells, and becomes highly activated whenever these cells are stimulated. Once activated Syk changes the activity of many proteins, affecting which genes are switched on and how the B cell moves and divides. By using DPP9 as a kind of bait, Justa-Schuch et al. found human proteins that bind to the protease. This search identified a protein called Filamin A that interacted with DPP9, placing DPP9 close to Syk, which also binds to Filamin A. Further experiments showed that when DPP9 was located close to Syk, it cut the end of Syk. This cut left the Syk protein with a different amino acid exposed at its end, which in turn made it susceptible to being broken down inside the cell. Justa-Schuch et al. went on to show that DPP9 preferentially cleaved the active form of Syk. Since cleaved Syk was subsequently broken down, DPP9 acts as a shut-off mechanism for Syk after the B cell has been stimulated. The findings show that DPP9 can influence how much and how long the B cell responds to stimulation. Inhibitors of DPP9 may therefore be useful for stabilizing Syk, which is known to stop specific tumors from growing. Future work will investigate the mechanisms that control how Filamin A, DPP9 and Syk interact."],["dc.identifier.doi","10.7554/eLife.16370"],["dc.identifier.isi","000385399800001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13846"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86123"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elife Sciences Publications Ltd"],["dc.relation.eissn","2050-084X"],["dc.relation.issn","2050-084X"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk"],["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.artnumber","A72"],["dc.bibliographiccitation.issue","Suppl 1"],["dc.bibliographiccitation.journal","Cell Communication and Signaling"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Engelke, M."],["dc.contributor.author","Hartig, R."],["dc.contributor.author","Goldbeck, I."],["dc.contributor.author","Manno, B."],["dc.contributor.author","Stirnweiß, A."],["dc.contributor.author","Zuschratter, W."],["dc.contributor.author","Schraven, B."],["dc.contributor.author","Wienands, J."],["dc.date.accessioned","2011-04-15T08:55:41Z"],["dc.date.accessioned","2021-10-27T13:22:37Z"],["dc.date.available","2011-04-15T08:55:41Z"],["dc.date.available","2021-10-27T13:22:37Z"],["dc.date.issued","2009"],["dc.identifier.doi","10.1186/1478-811X-7-S1-A72"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6144"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92111"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Real time monitoring of B cell antigen receptor-proximal events by fluorescence lifetime imaging"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["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"]]