Wienands, Jürgen

[["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","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.issue","5"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.volume","183"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T11:25:03Z"],["dc.date.available","2018-11-07T11:25:03Z"],["dc.date.issued","2009"],["dc.format.extent","2891"],["dc.identifier.doi","10.4049/jimmunol.0990063"],["dc.identifier.isi","000269391400001"],["dc.identifier.pmid","19696426"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56544"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","0022-1767"],["dc.title","Comment on \"Direct Hematological Toxicity and Illegitimate Chromosomal Recombination Caused by the Systemic Activation of CreER(T2)\""],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","652"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part A"],["dc.bibliographiccitation.lastpage","658"],["dc.bibliographiccitation.volume","158A"],["dc.contributor.author","Pauli, Silke"],["dc.contributor.author","Steinemann, Doris"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Shoukier, Moneef"],["dc.contributor.author","Moeschner, Marita"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Manukjan, Georgi"],["dc.contributor.author","Goehring, Gudrun"],["dc.contributor.author","Escherich, Gabriele"],["dc.date.accessioned","2018-11-07T09:12:38Z"],["dc.date.available","2018-11-07T09:12:38Z"],["dc.date.issued","2012"],["dc.description.abstract","Noonan syndrome (NS) is a common autosomal dominant condition characterized by short stature, congenital heart defects, and dysmorphic facial features caused in approximately 50% of cases by missense mutations in the PTPN11 gene. NS patients are predisposed to malignancies including myeloproliferative disorders or leukemias. We report a female NS patient carrying a PTPN11 germline mutation c.417 G?>?C (p.E139D), who developed in her second year of life an acute lymphoblastic leukemia (ALL) and after remission, she developed at 4 years of age a juvenile myelomonocytic leukemia (JMML). Molecular genetic analysis of lymphoblastic blasts at the time of the ALL diagnosis revealed the germline mutation in a heterozygous state, while in the myelomonocytic blasts occurring with JMML diagnosis, the mutation p.E139D was found in a homozygous state due to a uniparental disomy (UPD). These findings lead to the suggestion that the pathogenesis of ALL and JMML in our patient is due to different mechanisms including somatically acquired secondary chromosomal abnormalities. (c) 2012 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/ajmg.a.34439"],["dc.identifier.isi","000300498500028"],["dc.identifier.pmid","22315187"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26985"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1552-4825"],["dc.title","Occurrence of acute lymphoblastic leukemia and juvenile myelomonocytic leukemia in a patient with Noonan syndrome carrying the germline PTPN11 mutation p.E139D"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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"]]

[["dc.bibliographiccitation.artnumber","8575"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Lutz, Johannes"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Boesl, Michael R."],["dc.contributor.author","Winkler, Thomas H."],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Engels, Niklas"],["dc.date.accessioned","2018-11-07T09:50:27Z"],["dc.date.available","2018-11-07T09:50:27Z"],["dc.date.issued","2015"],["dc.description.abstract","Secondary antibody responses are marked by faster kinetics, improved antibody affinity and a switch from IgM to other immunoglobulin isotypes, most notably IgG, compared with primary responses. These changes protect from reinfection and represent the principle of most vaccination strategies. Yet, the molecular mechanisms that underlie B-cell memory responses are unclear. Here we show, by inactivating the immunoglobulin tail tyrosine (ITT) signalling motif of membrane-bound IgG1 in the mouse, that the ITT facilitates maintenance and reactivation of IgG-switched memory B cells in vivo. The ITT motif equips IgG-switched cells with enhanced BCR signalling capacity, which supports their competitiveness in secondary immune reactions and drives the formation of IgG-secreting plasma cells even in the absence of T-cell help. Our results demonstrate that ITT signalling promotes the vigorous production of IgG antibodies and thus provide a molecular basis for humoral immunological memory."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG) [EN 834/1-1, EN 834/2-1, TRR130]"],["dc.identifier.doi","10.1038/ncomms9575"],["dc.identifier.isi","000364932600022"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12791"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35716"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Reactivation of IgG-switched memory B cells by BCR-intrinsic signal amplification promotes IgG antibody production"],["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","41"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.lastpage","58"],["dc.bibliographiccitation.volume","210"],["dc.contributor.author","Schneppenheim, Janna"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Huettl, Susann"],["dc.contributor.author","Luellmann-Rauch, Renate"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Eskelinen, Eeva-Liisa"],["dc.contributor.author","Hermans-Borgmeyer, Irm"],["dc.contributor.author","Fluhrer, Regina"],["dc.contributor.author","Saftig, Paul"],["dc.contributor.author","Schroeder, Bernd"],["dc.date.accessioned","2018-11-07T09:29:12Z"],["dc.date.available","2018-11-07T09:29:12Z"],["dc.date.issued","2013"],["dc.description.abstract","Regulated intramembrane proteolysis is a central cellular process involved in signal transduction and membrane protein turnover. The presenilin homologue signal-peptide-peptidase-like 2a (SPPL2a) has been implicated in the cleavage of type 2 transmembrane proteins. We show that the invariant chain (li, CD74) of the major histocompatability class II complex (MHCII) undergoes intramembrane proteolysis mediated by SPPL2a. B lymphocytes of SPPL2a(-/-) mice accumulate an N-terminal fragment (NTF) of CD74, which severely impairs membrane traffic within the endocytic system and leads to an altered response to B cell receptor stimulation, reduced BAFF-R surface expression, and accumulation of MHCII in transitional developmental stage T1 B cells. This results in significant loss of B cell subsets beyond the T1 stage and disrupted humoral immune responses, which can be recovered by additional ablation of CD74. Hence, we provide evidence that regulation of CD74-NTF levels by SPPL2a is indispensable for B cell development and function by maintaining trafficking and integrity of MHCII-containing endosomes, highlighting SPPL2a as a promising pharmacological target for depleting and/or modulating B cells."],["dc.identifier.isi","000313560900006"],["dc.identifier.pmid","23267015"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30966"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Rockefeller Univ Press"],["dc.relation.issn","0022-1007"],["dc.title","The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","134"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Gastroenterology"],["dc.bibliographiccitation.lastpage","U256"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Pelczar, Penelope"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","van Dop, Willemijn A."],["dc.contributor.author","Heijmans, Jarom"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Gruber, Wolfgang"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Guijarro, Maria V."],["dc.contributor.author","Hernando, Eva"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Wojnowski, Leszek"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Taguchi, Takahiro"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Hogendoorn, Pancras Cornelis Wilhelmus"],["dc.contributor.author","Antonescu, Cristina R."],["dc.contributor.author","Rubin, Brian P."],["dc.contributor.author","Schulz-Schaeffer, Walter Joachim"],["dc.contributor.author","Aberger, Fritz"],["dc.contributor.author","van den Brink, Gijs R."],["dc.contributor.author","Hahn, Heidi Eva"],["dc.date.accessioned","2018-11-07T09:30:42Z"],["dc.date.available","2018-11-07T09:30:42Z"],["dc.date.issued","2013"],["dc.description.abstract","BACKGROUND & AIMS: A fraction of gastrointestinal stromal tumor (GIST) cells overexpress the platelet-derived growth factor receptor (PDGFR) A, although most overexpress KIT. It is not known if this is because these receptor tyrosine kinases have complementary oncogenic potential, or because of heterogeneity in the cellular origin of GIST. Little also is known about why Hedgehog (HH) signaling is activated in some GIST. HH binds to and inactivates the receptor protein patched homolog (PTCH). METHODS: Ptch was conditionally inactivated in mice (to achieve constitutive HH signaling) using a Cre recombinase regulated by the lysozyme M promoter. Cre-expressing cells were traced using R26R-LacZ reporter mice. Tumors were characterized by in situ hybridization, immunohistochemistry, immunoblot, and quantitative reverse-transcriptase polymerase chain reaction analyses. Cell transformation was assessed by soft agar assay. RESULTS: Loss of Ptch from lysozyme M-expressing cells resulted in the development of tumors of GIST-like localization and histology; these were reduced when mice were given imatinib, a drug that targets KIT and PDGFRA. The Hh signaling pathway was activated in the tumor cells, and Pdgfr alpha, but not Kit, was overexpressed and activated. Lineage tracing revealed that Cre-expressing intestinal cells were Kit-negative. These cells sometimes expressed Pdgfr alpha and were located near Kit-positive interstitial cells of Cajal. In contrast to KIT, activation of PDGFRA increased anchorage-independent proliferation and was required for tumor formation in mice by cells with activated HH signaling. CONCLUSIONS: Inactivation of Ptch in mice leads to formation of GIST-like tumors that express Pdgfr alpha, but not Kit. Activation of Pdgfr alpha signaling appears to facilitate tumorigenesis."],["dc.identifier.doi","10.1053/j.gastro.2012.09.061"],["dc.identifier.isi","000312965100034"],["dc.identifier.pmid","23041331"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31367"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","0016-5085"],["dc.title","Inactivation of Patched1 in Mice Leads to Development of Gastrointestinal Stromal-Like Tumors That Express Pdgfr alpha but Not Kit"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","29059"],["dc.bibliographiccitation.issue","39"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","29066"],["dc.bibliographiccitation.volume","282"],["dc.contributor.author","Abudula, Abulizi"],["dc.contributor.author","Grabbe, Annika"],["dc.contributor.author","Brechmann, Markus"],["dc.contributor.author","Polaschegg, Christian"],["dc.contributor.author","Herrmann, Nadine"],["dc.contributor.author","Goldbeck, Ingo"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.date.accessioned","2018-11-07T10:58:27Z"],["dc.date.available","2018-11-07T10:58:27Z"],["dc.date.issued","2007"],["dc.description.abstract","The family of SLPs ((S) under bar rc homology 2 domain-containing (l) under bar eukocyte adaptor (p) under bar roteins) are cytoplasmic signal effectors of lymphocyte antigen receptors. A main function of SLP is to orchestrate the assembly of Ca2+-mobilizing enzymes at the inner leaflet of the plasma membrane. For this purpose, SLP-76 in T cells utilizes the transmembrane adaptor LAT, but the mechanism of SLP-65 membrane anchoring in B cells remains an enigma. We now employed two genetic reconstitution systems to unravel structural requirements of SLP-65 for the initiation of Ca2+ mobilization and subsequent activation of gene transcription. First, mutational analysis of SLP-65 in DT40 B cells revealed that its C-terminal Src homology 2 domain controls efficient tyrosine phosphorylation by the kinase Syk, plasma membrane recruitment, as well as downstream signaling to NFAT activation. Second, we dissected these processes by expressing SLP-65 in SLP-76-deficient T cells and found that a kinase-independent adaptor function of Syk is required to link phosphorylated SLP-65 to Ca2+ mobilization. These approaches unmask a mechanistic complexity of SLP-65 activation and coupling to signaling cascades in that Syk is upstream as well as downstream of SLP-65. Moreover, membrane anchoring of the SLP-65-assembled Ca2+ initiation complex, which appears to be fundamentally different from that of closely related SLP-76, does not necessarily involve a B cell-specific component."],["dc.identifier.doi","10.1074/jbc.M704043200"],["dc.identifier.isi","000249642100080"],["dc.identifier.pmid","17681949"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50483"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","SLP-65 signal transduction requires Src homology 2 domain-mediated membrane anchoring and a kinase-independent adaptor function of Syk"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]