Proteomics

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Phosphorylation of the multi functional signal transducer B-cell adaptor protein (BCAP) facilitates recruitment of multiple SH2/SH3 proteins including Grb2.


ABSTRACT: B-cell adaptor protein (BCAP) is a multimodular, multi-functional signal transducer that regulates signal transduction processes in leukocytes including macrophages, B-cells and T-cells. In particular BCAP acts as a negative regulator of inflammatory signaling by the Toll-like receptors. Here we characterize the complex phosphorylation patterns of BCAP and use a novel protein complex trapping strategy (virotrap) to identify interaction partners. This analysis identifies known interactions with BCAP with PI3K p85 subunit and Nck, together with novel SH2 and SH3 domain adaptor proteins notably Grb2 and CRKL. We show that the SH3 domain of Grb2 can bind to BCAP independently of phosphorylation, suggesting that the SH2 domains mediate interaction with activated receptor tyrosine kinase complexes including the CD19 subunit of the B-cell receptor. Our data also suggest that PI3K p85 subunit binds to the BCAP via SH3 domains forming an inactive complex that is activated subsequently by sequential binding with the SH2 domains. Taken together our results indicate that BCAP is a complex hub that processes signals from multiple pathways in diverse immune system cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Sven Eyckerman  

LAB HEAD: Sven Eyckerman

PROVIDER: PXD014410 | Pride | 2019-09-16

REPOSITORIES: Pride

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Publications

Phosphorylation of the multifunctional signal transducer B-cell adaptor protein (BCAP) promotes recruitment of multiple SH2/SH3 proteins including GRB2.

Lauenstein Johannes U JU   Udgata Atul A   Bartram Alex A   De Sutter Delphine D   Fisher David I DI   Halabi Samer S   Eyckerman Sven S   Gay Nicholas J NJ  

The Journal of biological chemistry 20190916 52


B-cell adaptor protein (BCAP) is a multimodular, multifunctional signal transducer that regulates signal transduction pathways in leukocytes, including macrophages, B-cells, and T-cells. In particular, BCAP suppresses inflammatory signaling by Toll-like receptors (TLRs). However, how BCAP itself is regulated and what its interaction partners are is unclear. Here, using human immune cell lines, including THP-1 cells, we characterized the complex phosphorylation patterns of BCAP and used a novel p  ...[more]

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