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

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