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The B‐cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85
Author(s) -
Oellerich Thomas,
Bremes Vanessa,
Neumann Konstantin,
Bohnenberger Hanibal,
Dittmann Kai,
Hsiao HeHsuan,
Engelke Michael,
Schnyder Tim,
Batista Facundo D,
Urlaub Henning,
Wienands Jürgen
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.251
Subject(s) - biology , breakpoint cluster region , syk , b cell receptor , microbiology and biotechnology , signal transduction , phosphorylation , immunoprecipitation , receptor , tyrosine kinase , b cell , immunology , biochemistry , antibody
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.