PKC-beta controls I kappa B kinase lipid raft recruitment and activation in response to BCR signaling.

Abstract

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.

• Authors: Thomas T Su, Beichu Guo, Yuko Kawakami, Karen Sommer, Keun Chae, Lisa A Humphries, Roberta M Kato, Shin Kang, Lisa Patrone, Randolph Wall, Michael Teitell, Michael Leitges, Toshiaki Kawakami, David J Rawlings
• Journal: Nature immunology (Nat Immunol) Vol. 3 Issue 8 Pg. 780-6 (Aug 2002) ISSN: 1529-2908 [Print] United States
• PMID: 12118249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 5,21 - 12,17-dimetheneo-18H-dibenzo(i,o)pyrrolo(3,4-1)(1,8)diazacyclohexandecine-18,10(19H)dione,8((dimethylamino)methyl)-6,7,8,9,10,11-hexahydro,monomethanesulfonate
• Enzyme Inhibitors
• I-kappa B Proteins
• Indoles
• Isoenzymes
• Maleimides
• Mesylates
• NF-kappa B
• Pyrroles
• Receptors, Antigen, B-Cell
• Ro 31-8425
• Protein Serine-Threonine Kinases
• Chuk protein, mouse
• I-kappa B Kinase
• Ikbkb protein, mouse
• Ikbke protein, mouse
• Protein Kinase C
• Protein Kinase C beta

Topics

• Animals
• Apoptosis (immunology)
• B-Lymphocytes (enzymology, immunology)
• Enzyme Inhibitors (pharmacology)
• Flow Cytometry
• I-kappa B Kinase
• I-kappa B Proteins (immunology)
• Immunoblotting
• Indoles (pharmacology)
• Isoenzymes (antagonists & inhibitors, 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, immunology)
• Protein Kinase C beta
• Protein Serine-Threonine Kinases (immunology, metabolism)
• Pyrroles (pharmacology)
• Receptors, Antigen, B-Cell (immunology)
• Signal Transduction (immunology)