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Molecular and Cellular Biology, October 2001, p. 6640-6650, Vol. 21, No. 19
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.19.6640-6650.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
B-Cell Receptor- and Phorbol Ester-Induced NF-
B
and c-Jun N-Terminal Kinase Activation in B Cells Requires Novel
Protein Kinase C's
Daniel
Krappmann,*
Alina
Patke,
Vigo
Heissmeyer,
and
Claus
Scheidereit
Max-Delbrück-Centrum for Molecular
Medicine, 13125 Berlin, Germany
Received 23 March 2001/Returned for modification 30 May
2001/Accepted 2 July 2001
Antigen receptor signaling is known to activate NF-
B in
lymphocytes. While T-cell-receptor-induced NF-
B activation
critically depends on novel protein kinase C
(PKC
), 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
and
but only weak expression of the
isoform. Rottlerin blocks
phorbol ester (phorbol myristate acetate [PMA])- or B-cell receptor
(BCR)-mediated NF-
B 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-
B
activation in B cells. Similar to the situation in splenic B cells,
rottlerin inhibits BCR and PMA stimulation of NF-
B in 70Z/3 cells. A
derivative of 70Z/3 cells, 1.3E2 cells, are defective in NF-
B
activation due to the lack of the I
B kinase (IKK
) protein. Ectopic expression of IKK
can rescue NF-
B activation in response to lipopolysaccharides (LPS) and interleukin-1
(IL-1
), 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
was absent in 1.3E2 cells while it was expressed in 70Z/3 cells.
Stable expression of either novel PKC
or -
but not classical PKC
II in 1.3E2 IKK
-expressing cells rescues PMA activation of NF-
B and JNK signaling, demonstrating a critical role of novel PKCs
for B-cell activation.
*
Corresponding author. Mailing address:
Max-Delbrück-Centrum for Molecular Medicine, Robert-Rössle
Str. 10, 13125 Berlin, Germany. Phone: 49-30-9406-3751. Fax:
49-30-9406-3866. E-mail: dkrapp{at}mdc-berlin.de.

Present address: Center for Blood Research, Harvard Medical School,
Boston, MA
02115.
Molecular and Cellular Biology, October 2001, p. 6640-6650, Vol. 21, No. 19
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.19.6640-6650.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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