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Nat Immunol. 2002 Aug;3(8):780-6. Epub 2002 Jul 15.

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

Author information

1
The Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.

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.

PMID:
12118249
DOI:
10.1038/ni823
[Indexed for MEDLINE]

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