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Molecular and Cellular Biology, August 1999, p. 5608-5618, Vol. 19, No. 8
Graduate Program in
Immunology1 and Department of Molecular
Microbiology & Immunology,2 The Johns
Hopkins University School of Public Health, Baltimore, Maryland 21205
Received 11 December 1998/Returned for modification 2 February
1999/Accepted 20 May 1999
Using a subtractive cloning scheme on cDNA prepared from primary
pro-B and pre-B cells, we identified several genes whose products
regulate apoptosis. We further characterized one of these genes,
encoding protein kinase C
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Copyright © 1999, American Society for Microbiology. All rights reserved.
Pro-B-Cell-Specific Transcription and
Proapoptotic Function of Protein Kinase C
(PKC
). PKC
transcripts were readily
detected in pro-B cells but were absent in pre-B cells. Although both a
full-length and a truncated form of PKC
were detectable in bone
marrow pro-B cells, transition to the pre-B-cell stage was associated
with increased relative levels of truncated PKC
. We found that
PKC
is proteolyzed in apoptotic lymphocytes, generating a
kinase-active fragment identical to the truncated form which is capable
of inducing apoptosis when expressed in a pro-B cell line. Caspase-3
can generate an identical PKC
cleavage product in vitro, and caspase
inhibitors prevent the generation of this product during apoptosis in
transfected cell lines. Inducible overexpression of either the
full-length or truncated form of PKC
results in cell cycle arrest at
the G1/S transition. These results suggest that the
expression and proteolytic activation of PKC
play an important role
in the regulation of cell division and cell death during early B-cell development.
*
Corresponding author. Present address: Department of
Molecular and Cell Biology, LSA 439, University of California,
Berkeley, CA 94720. Phone: (510) 643-2462. E-mail:
mss{at}uclink4.berkeley.edu.edu.
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