TableEdit

Su, TT, Guo, B, Kawakami, Y, Sommer, K, Chae, K, Humphries, LA, Kato, RM, Kang, S, Patrone, L, Wall, R, Teitell, M, Leitges, M, Kawakami, T and Rawlings, DJ (2002) PKC-beta controls I kappa B kinase lipid raft recruitment and activation in response to BCR signaling. Nat. Immunol. 3:780-6

NF-kappa B signaling is required for the maintenance of normal B lymphocytes, whereas dysregulated NF-kappa B activation contributes to B cell lymphomas. The events that regulate NF-kappa B signaling in B lymphocytes are poorly defined. Here, we demonstrate that PKC-beta is specifically required for B cell receptor (BCR)-mediated NF-kappa B activation. B cells from protein kinase C-beta (PKC-beta)-deficient mice failed to recruit the I kappa B kinase (IKK) complex into lipid rafts, activate IKK, degrade I kappa B or up-regulate NF-kappa B-dependent survival signals. Inhibition of PKC-beta promoted cell death in B lymphomas characterized by exaggerated NF-kappa B 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.

PubMed Online version:10.1038/ni823

Animals; Apoptosis/immunology; B-Lymphocytes/enzymology; B-Lymphocytes/immunology; Enzyme Inhibitors/pharmacology; Flow Cytometry; I-kappa B Kinase; I-kappa B Proteins/immunology; Immunoblotting; Indoles/pharmacology; Isoenzymes/antagonists & inhibitors; Isoenzymes/immunology; Lymphoma, B-Cell/immunology; Maleimides/pharmacology; Mesylates/pharmacology; Mice; Mice, Inbred BALB C; Mice, Knockout; NF-kappa B/immunology; Protein Kinase C/antagonists & inhibitors; Protein Kinase C/immunology; Protein-Serine-Threonine Kinases/immunology; Protein-Serine-Threonine Kinases/metabolism; Pyrroles/pharmacology; Receptors, Antigen, B-Cell/immunology; Signal Transduction/immunology