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The AKT kinase signaling network is rewired by PTEN to control proximal BCR signaling in germinal center B cells.

Nat. Immunol.. 2019-06; 
LuoWei,HawseWilliam,ConterLaura,TrivediNikita,WeiselFlorian,WikenheiserDaniel,CattleyRichard T,ShlomchikMa
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Molecular Biology Reagents Endotoxin was removed from antibodies used for stimulation with ToxinEraser Endotoxin Removal Kit (GenScript) and endotoxin levels were tested with an LAL assay kit (GenScript) (endotoxin<0.5EUml−1 ). Get A Quote

摘要

B cell antigen receptor (BCR) and CD40 signaling are rewired in germinal center (GC) B cells (GCBCs) to optimize selection for high-affinity B cells. In GCBC, BCR signals are constrained, but the mechanisms are not well understood. Here we describe a GC-specific, AKT-kinase-driven negative feedback loop that attenuates BCR signaling. Mass spectrometry revealed that AKT target activity was altered in GCBCs compared with naive B cells. Retargeting was linked to differential AKT T308 and S473 phosphorylation, in turn controlled by GC-specific upregulation of phosphoinositide-dependent protein kinase PDK1 and the phosphatase PTEN. In GCBCs, AKT preferentially targeted CSK, SHP-1 and HPK1, which are ne... More

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