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Publication : Endocytosed BCRs sequentially regulate MAPK and Akt signaling pathways from intracellular compartments.

First Author  Chaturvedi A Year  2011
Journal  Nat Immunol Volume  12
Issue  11 Pages  1119-26
PubMed ID  21964606 Mgi Jnum  J:177665
Mgi Id  MGI:5295805 Doi  10.1038/ni.2116
Citation  Chaturvedi A, et al. (2011) Endocytosed BCRs sequentially regulate MAPK and Akt signaling pathways from intracellular compartments. Nat Immunol 12(11):1119-26
abstractText  Binding of antigen to the B cell antigen receptor (BCR) triggers both BCR signaling and endocytosis. How endocytosis regulates BCR signaling remains unknown. Here we report that BCR signaling was not extinguished by endocytosis of BCRs; instead, BCR signaling initiated at the plasma membrane continued as the BCR trafficked intracellularly with the sequential phosphorylation of kinases. Blocking the endocytosis of BCRs resulted in the recruitment of both proximal and downstream kinases to the plasma membrane, where mitogen-activated protein kinases (MAPKs) were hyperphosphorylated and the kinase Akt and its downstream target Foxo were hypophosphorylated, which led to the dysregulation of gene transcription controlled by these pathways. Thus, the cellular location of the BCR serves to compartmentalize kinase activation to regulate the outcome of signaling.
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