Project Details
Regulation der biphasischen Ca2+-Mobilisierung in aktivierten B-Zellen
Applicant
Professor Dr. Jürgen Wienands
Subject Area
Immunology
Term
from 2003 to 2012
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5470521
Final Report Year
2014
Final Report Abstract
Ziel des Teilprojektes 3 war es, B-Zell-Antigenrezeptor (BCR)-proximale Signalprozesse zu charakterisieren und Regulationsmechanismen zu identifizieren, die eine kontrollierte Entwicklung und Aktivierung von B-Zellen ermöglichen. Wir haben dieses Ziel erreicht und konnten unter anderem mit Dok-3/Grb2 und Cin85 wichtige BCR-proximale Schaltelemente identifizieren sowie ihre Steuerungsfunktion in BCR-Signalosomen detailliert beschreiben. Zudem haben wir massenspektrometrische und bildgebende Verfahren entwickelt, mit deren Hilfe wir die Kinetik und Dynamik komplexer Protein-Protein-Interaktionen während der BCR-Signalweiterleitung analysiert haben.
Publications
- (2007) Ca(2+) signaling in antigen receptor-activated B lymphocytes. Immunological reviews 218: 235-246
Engelke M, Engels N, Dittmann K, Stork B, Wienands J
- (2007) Subcellular localization of Grb2 by the adaptor protein Dok-3 restricts the intensity of Ca2+ signaling in B cells. Embo J 26: 1140-1149
Stork B, Neumann K, Goldbeck I, Alers S, Kahne T, Naumann M, Engelke M, Wienands J
- (2009) SLP-65 phosphorylation dynamics reveals a functional basis for signal integration by receptor-proximal adaptor proteins. Molecular & Cellular Proteomics: MCP 8: 1738 1750
Oellerich T, Gronborg M, Neumann K, Hsiao HH, Urlaub H, Wienands J
- (2009) The B-lymphoid Grb2 interaction code. Immunological reviews 232: 135-149
Neumann K, Oellerich T, Urlaub H, Wienands J
- (2010). Non-T cell activation linker regulates ERK activation in Helicobacter pylori-infected epithelial cells. Cell Signal 22:395-403
Rieke, C., Kahne, T., Schweitzer, K., Schraven, B., Wienands, J., Engelke, M. and Naumann, M.
- (2011) B cell receptor-mediated antigen gathering requires ubiquitin ligase Cbl and adaptors Grb2 and Dok-3 to recruit dynein to the signaling microcluster. Immunity 34: 905-918
Schnyder T, Castello A, Feest C, Harwood NE, Oellerich T, Urlaub H, Engelke M, Wienands J, Bruckbauer A, Batista FD
- (2011) Complex phosphorylation dynamics control the composition of the Syk interactome in B cells. European Journal of Immunology 41: 1550-1562
Bohnenberger H, Oellerich T, Engelke M, Hsiao HH, Urlaub H, Wienands J
- (2011) Fc gamma receptor IIb modulates the molecular Grb2 interaction network in activated B cells. Cellular signalling 23: 893-900
Neumann K, Oellerich T, Heine I, Urlaub H, Engelke M
- (2011) The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85. The EMBO journal 30: 3620-3634
Oellerich T, Bremes V, Neumann K, Bohnenberger H, Dittmann K, Hsiao HH, Engelke M, Schnyder T, Batista FD, Urlaub H, Wienands J
- (2012) Spatiotemporal resolution of Ca(2+) signaling events by real time imaging of single B cells. FEBS letters 586: 1452-1458
Junek S, Engelke M, Schild D, Wienands J
(See online at https://doi.org/10.1016/j.febslet.2012.03.057) - (2013) Cutting Edge: Feed Forward Activation of Phospholipase Cgamma2 via C2 Domain-Mediated Binding to SLP65. Journal of immunology. [Epub ahead of print]
Engelke M, Oellerich T, Dittmann K, Hsiao HH, Urlaub H, Serve H, Griesinger C, Wienands J
(See online at https://doi.org/10.4049/jimmunol.1301326) - (2013) Nckmediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells. Nature immunology 14: 966-975
Castello A, Gaya M, Tucholski J, Oellerich T, Lu KH, Tafuri A, Pawson T, Wienands J, Engelke M, Batista FD
(See online at https://doi.org/10.1038/ni.2685) - (2013) The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation of Syk kinase in B cell antigen receptor microclusters. The Journal of biological chemistry 288: 2303-2313
Losing M, Goldbeck I, Manno B, Oellerich T, Schnyder T, Bohnenberger H, Stork B, Urlaub H, Batista FD, Wienands J, Engelke M
(See online at https://doi.org/10.1074/jbc.M112.406546)