PKC-β controls IκB kinase lipid raft recruitment and activation in response to BCR signaling

NF-κB signaling is required for the maintenance of normal B lymphocytes, whereas dysregulated NF-κB activation contributes to B cell lymphomas. The events that regulate NF-κB signaling in B lymphocytes are poorly defined. Here, we demonstrate that PKC-β is specifically required for B cell receptor (BCR)-mediated NF-κB activation. B cells from protein kinase C-β (PKC-β)-deficient mice failed to recruit the IκB kinase (IKK) complex into lipid rafts, activate IKK, degrade IκB or up-regulate NF-κB–dependent survival signals. Inhibition of PKC-β promoted cell death in B lymphomas characterized by exaggerated NF-κB activity. Together, these data define an essential role for PKC-β in BCR survival signaling and highlight PKC-β as a key therapeutic target for B-lineage malignancies.