Using a subtractive cloning scheme on cDNA prepared from primary pro-B and
pre-B cells, we identified several genes whose produces regulate apoptosis.
We further characterized one of these genes, encoding protein kinase C eta
(PKC eta). PKC eta transcripts were readily detected in pro-B cells but we
re absent in pre-B cells. Although both a full-length and a truncated form
of PKC eta were detectable in bone marrow pro-B cells, transition to the pr
e-B-cell stage was associated with increased relative levels of truncated P
KC eta; We found that PKC eta is proteolyzed in apoptotic lymphocytes, gene
rating a kinase-active fragment identical to the truncated form which is ca
pable of inducing apoptosis when expressed in a pro-B cell line. Caspase-3
can generate an identical PKC eta cleavage product in vitro, and caspase in
hibitors prevent the generation of this product during apoptosis in transfe
cted cell lines. Inducible overexpression of either the full-length or trun
cated form of PKC eta results in cell cycle arrest at the G(1)/S transition
. These results suggest that the expression and proteolytic activation of P
KC eta play an important role in the regulation of cell division and cell d
eath during early B-cell development.