Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 21, Issue 19, Pages 6640-6650Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.21.19.6640-6650.2001
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Antigen receptor signaling is known to activate NF-kappaB in lymphocytes. While T-cell-receptor-indticed NF-kappaB activation critically depends on novel protein kinase C theta (PKC theta), the role of novel PKCs in B-cell stimulation has not been elucidated. In primary murine splenic B cells, we found high expression of the novel PKCs delta and epsilon but only weak expression of the theta isoform. Rottlerin blocks phorbol ester (phorbol myristate acetate [PMA])or B-cell receptor (BCR)-mediated NF-kappaB and c-Jun N-terminal kinase (JNK) activation in primary B and T cells to a similar extent, suggesting that novel PKCs are positive regulators of signaling in hematopoietic cells. Mouse 70Z/3 pre-B cells have been widely used as a model for NF-kappaB activation in B cells. Similar to the situation in splenic B cells, rottlerin inhibits BCR and PMA stimulation of NF-kappaB in 70Z/3 cells. A derivative of 70Z/3 cells, 1.3E2 cells, are defective in NF-kappaB activation due to the lack of the I kappaB kinase (IKK gamma) protein. Ectopic expression of IKK gamma can rescue NF-kappaB activation in response to lipopolysaccharides (LPS) and interleukin-1 beta (IL-1 beta), but not to PMA. In addition, PMA-induced activation of the mitogen-activated protein kinase JNK is blocked in 1.3E2 cells, suggesting that an upstream component common to both pathways is either missing or mutated. Analysis of various PKC isoforms revealed that exclusively PKC theta was absent in 1.3E2 cells while it was expressed in 70Z/3 cells. Stable expression of either novel PKC theta or -delta but not classical PKC beta II in 1.3E2 IKK gamma -expressing cells rescues PMA activation of NF-kappaB and JNK signaling, demonstrating a critical role of novel PKCs for B-cell activation.
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