Engelke, Michael

[["dc.bibliographiccitation.firstpage","1398"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","1411"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Schneppenheim, Janna"],["dc.contributor.author","Huettl, Susann"],["dc.contributor.author","Mentrup, Torben"],["dc.contributor.author","Luellmann-Rauch, Renate"],["dc.contributor.author","Rothaug, Michelle"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Araki, Masatake"],["dc.contributor.author","Araki, Kimi"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Fluhrer, Regina"],["dc.contributor.author","Saftig, Paul"],["dc.contributor.author","Schroeder, Bernd"],["dc.date.accessioned","2018-11-07T09:42:09Z"],["dc.date.available","2018-11-07T09:42:09Z"],["dc.date.issued","2014"],["dc.description.abstract","We reported recently that the presenilin homologue signal peptide peptidase-like 2a (SPPL2a) is essential for B cell development by cleaving the N-terminal fragment (NTF) of the invariant chain (li, CD74). Based on this, we suggested that pharmacological modulation of SPPL2a may represent a novel approach to deplete B cells in autoimmune disorders. With regard to reported overlapping substrate spectra of SPPL2a and its close homologue, SPPL2b, we investigated the role of SPPL2b in CD74 NTF proteolysis and its impact on B and dendritic cell homeostasis. In heterologous expression experiments, SPPL2b was found to cleave CD74 NTF with an efficiency simliar to that of SPPL2a. For in vivo analysis, SPPL2b single-deficient and SPPL2a/SPPL2b double-deficient mice were generated and examined for CD74 NTF turnover/accumulation, B cell maturation and functionality, and dendritic cell homeostasis. We demonstrate that in vivo SPPL2b does not exhibit a physiologically relevant contribution to CD74 proteolysis in B and dendritic cells. Furthermore, we reveal that both proteases exhibit divergent subcellular localizations in B cells and different expression profiles in murine tissues. These findings suggest distinct functions of SPPL2a and SPPL2b and, based on a high abundance of SPPL2b in brain, a physiological role of this protease in the central nervous system."],["dc.identifier.doi","10.1128/MCB.00038-14"],["dc.identifier.isi","000333338600003"],["dc.identifier.pmid","24492962"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33889"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Microbiology"],["dc.relation.issn","1098-5549"],["dc.relation.issn","0270-7306"],["dc.title","The Intramembrane Proteases Signal Peptide Peptidase-Like 2a and 2b Have Distinct Functions In Vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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","1587"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Cancer Immunology Immunotherapy"],["dc.bibliographiccitation.lastpage","1597"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Koenig, Simone"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Schwendener, Reto"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T09:19:32Z"],["dc.date.available","2018-11-07T09:19:32Z"],["dc.date.issued","2013"],["dc.description.abstract","Liposomes are frequently used in cancer therapy to encapsulate and apply anticancer drugs. Here, we show that a systemic treatment of mice bearing skin tumors with empty phosphatidylcholine liposomes (PCL) resulted in inhibition of tumor growth, which was similar to that observed with the synthetic bacterial lipoprotein and TLR1/2 agonist Pam(3)CSK(4) (BLP). Both compounds led to a substantial decrease of macrophages in spleen and in the tumor-bearing skin. Furthermore, both treatments induced the expression of typical macrophage markers in the tumor-bearing tissue. As expected, BLP induced the expression of the M1 marker genes Cxcl10 and iNOS, whereas PCL, besides inducing iNOS, also increased the M2 marker genes Arg1 and Trem2. In vitro experiments demonstrated that neither PCL nor BLP influenced proliferation or survival of tumor cells, whereas both compounds inhibited proliferation and survival and increased the migratory capacity of bone marrow-derived macrophages (BMDM). However, in contrast to BLP, PCL did not activate cytokine secretion and induced a different BMDM phenotype. Together, the data suggest that similar to BLP, PCL induce an antitumor response by influencing the tumor microenvironment, in particular by functional alterations of macrophages, however, in a distinct manner from those induced by BLP."],["dc.description.sponsorship","DFG [FOR942 HA 2197/5-2]"],["dc.identifier.doi","10.1007/s00262-013-1444-4"],["dc.identifier.isi","000325008800005"],["dc.identifier.pmid","23917775"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28662"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0340-7004"],["dc.title","Empty liposomes induce antitumoral effects associated with macrophage responses distinct from those of the TLR1/2 agonist Pam(3)CSK(4) (BLP)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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.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.firstpage","235"],["dc.bibliographiccitation.journal","Immunological Reviews"],["dc.bibliographiccitation.lastpage","246"],["dc.bibliographiccitation.volume","218"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Engels, Niklas"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Stork, Bjorn"],["dc.contributor.author","Wienands, Juergen"],["dc.date.accessioned","2018-11-07T11:00:05Z"],["dc.date.available","2018-11-07T11:00:05Z"],["dc.date.issued","2007"],["dc.description.abstract","B cells respond to antigen stimulation with mobilization of the Ca2+ second messenger in two phases operated by two distinct sets of effector proteins. First, an antigen receptor-specific Ca2+ initiation complex is assembled, activated, and targeted to the plasma membrane to trigger the transient release of Ca2+ from intracellular stores of the endoplasmic reticulum. Second, more ubiquitously expressed Ca2+ channels of the plasma membrane are opened to allow for sustained Ca2+ influx from the extracellular medium. Depending on the developmental stage of the B cell, the kinetics and profile of the two phases are adjusted at multiple levels of positive and negative regulation. A molecular basis for the Ca2+ signaling plasticity is provided by cytosolic and transmembrane adapter proteins. They act as signal organizers, which control enzyme/substrate interactions by directing the different signaling modules into specific subcellular compartments. These arrangements orchestrate a graduated activation of Ca2+-sensitive downstream pathways, which ultimately determine appropriate cellular responses, namely elimination of autoreactive B cells or proliferation and differentiation of immunocompetent B cells into antibody-secreting plasma cells."],["dc.identifier.doi","10.1111/j.1600-065X.2007.00539.x"],["dc.identifier.isi","000247924700017"],["dc.identifier.pmid","17624956"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50851"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0105-2896"],["dc.title","Ca2+ signaling in antigen receptor-activated B lymphocytes"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]