In:
Nature Communications, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2016-08-24)
Abstract:
Crosslinking of B-cell receptor (BCR) sets off an apoptosis programme, but the underlying pathways remain obscure. Here we decipher the molecular mechanisms bridging B-cell activation and apoptosis mediated by post-translational modification (PTM). We find that O -GlcNAcase inhibition enhances B-cell activation and apoptosis induced by BCR crosslinking. This proteome-scale analysis of the functional interplay between protein O -GlcNAcylation and phosphorylation in stimulated mouse primary B cells identifies 313 O -GlcNAcylation-dependent phosphosites on 224 phosphoproteins. Among these phosphoproteins, temporal regulation of the O -GlcNAcylation and phosphorylation of lymphocyte-specific protein-1 (Lsp1) is a key switch that triggers apoptosis in activated B cells. O -GlcNAcylation at S209 of Lsp1 is a prerequisite for the recruitment of its kinase, PKC-β1, to induce S243 phosphorylation, leading to ERK activation and downregulation of BCL-2 and BCL-xL. Thus, we demonstrate the critical PTM interplay of Lsp1 that transmits signals for initiating apoptosis after BCR ligation.
Type of Medium:
Online Resource
ISSN:
2041-1723
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2016
detail.hit.zdb_id:
2553671-0
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