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- Title
PKC-B controls I?B kinase lipid raft recruitment and activation in response to BCR signaling.
- Authors
Su, Thomas T.; Guo, Beichu; Kawakami, Yuko; Sommer, Karen; Chae, Keun; Humphries, Lisa A.; Kato, Roberta M.; Kang, Shin; Patrone, Lisa; Wall, Randolph; Teitell, Michael; Leitges, Michael; Kawakami, Toshiaki; Rawlings, David J.
- Abstract
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.
- Subjects
NF-kappa B; TRANSCRIPTION factors; MOLECULAR immunology
- Publication
Nature Immunology, 2002, Vol 3, Issue 8, p780
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni823