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The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85.

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Oellerich, Thomas; Bremes, Vanessa; Neumann, Konstantin; Bohnenberger, Hanibal; Dittmann, Kai; Hsiao, He-Hsuan; Engelke, Michael; Schnyder, Tim; Batista, Facundo D.; Urlaub, Henning; Wienands, Jürgen (2011): The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85. - The EMBO journal; Vol. 30, No. 17, p. 3620-34.

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Web of Science® Times Cited:20

Verlagspublikation: 10.1038/emboj.2011.251

 
Author: Oellerich, Thomas; Bremes, Vanessa; Neumann, Konstantin; Bohnenberger, Hanibal; Dittmann, Kai; Hsiao, He-Hsuan; Engelke, Michael; Schnyder, Tim; Batista, Facundo D.; Urlaub, Henning; Wienands, Jürgen
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-κB 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.
URI: http://resolver.sub.uni-goettingen.de/purl?gs-1/7839
Date: 2011-08-31
Bemerkung: Our research received funding from the European Community’s Seventh Framework Program FP7/2007– 2013 under grant agreement no 201549 (EURO-PADnet HEALTH-F2- 2008-201549) and the Deutsche Forschungsgemeinschaft through FOR 521 and SFB 860.
EU Seventh Framework Programme Logo Project: EURO-PADNET Förderkennzeichen: 201549

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