The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85
| Autor: | Thomas, Oellerich, Vanessa, Bremes, Konstantin, Neumann, Hanibal, Bohnenberger, Kai, Dittmann, He-Hsuan, Hsiao, Michael, Engelke, Tim, Schnyder, Facundo D, Batista, Henning, Urlaub, Jürgen, Wienands |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
B-Lymphocytes
Molecular Sequence Data Intracellular Signaling Peptides and Proteins NF-kappa B Receptors Antigen B-Cell tyrosine kinase Nerve Tissue Proteins adaptor proteins Protein-Tyrosine Kinases proteome analysis Article Neoplasm Proteins Mice B-cell receptor Animals Humans Syk Kinase Calcium Amino Acid Sequence Phosphorylation Adaptor Proteins Signal Transducing Signal Transduction |
| Zdroj: | The EMBO Journal |
| ISSN: | 1460-2075 |
| Popis: | The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85 The Slp65 adaptor molecule is important for B-cell receptor signalling. Here, the interactomes of SLP65 in resting and activated B cells are resolved by mass spectrometry. A number of SLP65 interacting partners, including CIN85, continuously associate with SLP65 in a stimulation-independent manner. CIN85 recruits SLP65 to the membrane and it is required for SLP65 phosphorylation. 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 Ca2+ 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text